Journal of Hepatology
Volume 51, Issue 1 , Pages 187-211 , July 2009

Role of epigenetics in liver-specific gene transcription, hepatocyte differentiation and stem cell reprogrammation

  • Sarah Snykers

      Affiliations

    • Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
    • Corresponding Author InformationCorresponding author. Tel.: +32 02 4774518; fax: +32 02 4774582.
    • These authors are post doctoral research fellows of the Fund for Scientific Research Flanders (FWO-Vlaanderen) Belgium.
    • These authors are post doctoral research fellows of the Fund for Scientific Research Flanders (FWO-Vlaanderen) Belgium.
    • ,
  • Tom Henkens

      Affiliations

    • Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
    • These authors contributed equally to this work.
    • ,
  • Evelien De Rop

      Affiliations

    • Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
    • ,
  • Mathieu Vinken

      Affiliations

    • Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
    • These authors are post doctoral research fellows of the Fund for Scientific Research Flanders (FWO-Vlaanderen) Belgium.
    • ,
  • Joanna Fraczek

      Affiliations

    • Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
    • ,
  • Joery De Kock

      Affiliations

    • Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
    • ,
  • Evi De Prins

      Affiliations

    • Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
    • ,
  • Albert Geerts

      Affiliations

    • Department of Cell Biology, Vrije Universiteit Brussels, Brussels, Belgium
    • Deceased.
    • ,
  • Vera Rogiers

      Affiliations

    • Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
    • ,
  • Tamara Vanhaecke

      Affiliations

    • Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium
    • These authors are post doctoral research fellows of the Fund for Scientific Research Flanders (FWO-Vlaanderen) Belgium.

References 

  1. Papeleu P, Vanhaecke T, Rogiers V. Histone deacetylase inhibition: a differentiation therapy for cultured primary hepatocytes. Curr Enz Inhib. 2006;2:91–104
  2. Papeleu P, Loyer P, Vanhaecke T, Elaut G, Geerts A, Guguen-Guillouzo C, et al. Trichostatin A induces cell cycle arrests but does not induce apoptosis in primary cultures of mitogen-stimulated rat hepatocytes. J Hepatol. 2003;39:374–382
  3. Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez FJ, Talianidis I. Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev. 2006;20:2293–2305
  4. Akiyama TE, Gonzalez FJ. Regulation of P450 genes by liver-enriched transcription factors and nuclear receptors. Biochim Biophys Acta. 2003;1619:223–234
  5. Costa RH, Kalinichenko VV, Holterman AX, Wang X. Transcription factors in liver development, differentiation, and regeneration. Hepatology. 2003;38:1331–1347
  6. Turner BM. Reading signals on the nucleosome with a new nomenclature for modified histones. Nat Struct Mol Biol. 2005;12:110–112
  7. Wolffe AP, Guschin D. Review: chromatin structural features and targets that regulate transcription. J Struct Biol. 2000;129:102–122
  8. Wang GG, Allis CD, Chi P. Chromatin remodeling and cancer, part I: covalent histone modifications. Trends Mol Med. 2007;13:363–372
  9. Collas P. Epigenetic states in stem cells. Biochim Biophys Acta. 2008;[ahead of print]
  10. Dannenberg LO, Edenbergh HJ. Epigenetics of gene expression in human hepatoma cells: expression profiling the response to inhibition of DNA methylation and histone deacetylation. BMC Genomics. 2006;7:181
  11. Yamashita Y, Shimada M, Harimoto N, Rikimaru T, Shirabe K, Tanaka S, et al. Histone deacetylase inhibitor trichostatin A induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells. Int J Cancer. 2003;103:572–576
  12. Atkinson S, Armstrong L. Epigenetics in embryonic stem cells: regulation of pluripotency and differentiation. Cell Tissue Res. 2008;331:23–29
  13. Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature. 2007;447:425–432
  14. Yeo S, Jeong S, Kim J, Han JS, Han YM, Kang YK. Characterization of DNA methylation change in stem cell marker genes during differentiation of human embryonic stem cells. Biochem Biophys Res Commun. 2007;359:536–542
  15. Perry P, Sauer S, Billon N, Richardson WD, Spivakov M, Warnes G, et al. A dynamic switch in the replication timing of key regulator genes in embryonic stem cells upon neural induction. Cell Cycle. 2004;3:1645–1650
  16. Moggs JG, Goodman JL, Trosko JE, Roberts RA. Epigenetics and cancer: implications for drug discovery and safety assessment. Toxicol Appl Pharmacol. 2004;196:422–430
  17. Szyf M. DNA methylation and demethylation as targets for anticancer therapy. Biochemistry (Mosc). 2005;70:533–549
  18. Allis CD, Berger SL, Cote J, Dent S, Jenuwien T, Kouzarides T, et al. New nomenclature for chromatin-modifying enzymes. Cell. 2007;131:633–636
  19. Weidle UH, Grossmann A. Inhibition of histone deacetylases: a new strategy to target epigenetic modifications for anticancer treatment. Anticancer Res. 2000;20:1471–1485
  20. Grunstein M. Histone acetylation in chromatin structure and transcription. Nature. 1997;389:349–352
  21. Yang XJ, Seto E. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene. 2007;26:5310–5318
  22. Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 2007;26:5541–5552
  23. Minucci S, Pellici PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006;6:38–51
  24. Smith CL. A shifting paradigm: histone deacetylases and transcriptional activation. Bioessays. 2008;30:15–24
  25. Gray SG, Ekström TJ. The human histone deacetylase family. Exp Cell Res. 2001;262:75–83
  26. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nature Rev Drug Discov. 2006;5:769–784
  27. Mariadason JM. HDACs and HDAC inhibitors in colon cancer. Epigenetics. 2008;3:28–37
  28. Grozinger CM, Hassig CA, Schreiber SL. Three proteins define a class of human histone deacetylases related to yeast Hda1p. Proc Natl Acad Sci USA. 1999;96:4868–4873
  29. Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, et al. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature. 1999;401:188–193
  30. Yang XJ, Grégoire S. Class II histone deacetylases: from sequence to function, regulation, and clinical implication. Mol Cell Biol. 2005;25:2873–2884
  31. Zhang CL, McKinsey TA, Olsen EN. Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation. Mol Cell Biol. 2002;22:7302–7312
  32. Martin M, Kettmann R, Dequiedt F. Class IIa histone deacetylases: regulating the regulators. Oncogene. 2007;26:5450–5467
  33. Vega RB, Matsuda K, Oh J, Barbosa AC, Yang X, Meadows E, et al. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell. 2004;119:555–566
  34. Bolger TA, Yao TP. Intracellular trafficking of histone deacetylase 4 regulates neuronal cell death. J Neurosci. 2005;25:9544–9553
  35. Boyault C, Sadoel K, Pabion M, Khochbin S. HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination. Oncogene. 2007;26:5468–5476
  36. Schroeder TM, Kahler RA, Li X, Westendorf JJ. Histone deacetylase 3 interacts with runx2 to repress the osteocalcin promoter and regulate osteoblast differentiation. J Biol Chem. 2004;279:41998–42007
  37. Puri PL, Iezzi S, Stiegler P, Chen TT, Schiltz RL, Muscat GE, et al. Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis. Mol Cell. 2001;8:885–897
  38. Wilson AJ, Byun DS, Popova N, Murray LB, L’Italien K, Sowa Y, et al. Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J Biol Chem. 2006;281:13548–13558
  39. Farooq M, Sulochana KN, Pan X, To J, Sheng D, Gong Z, et al. Histone deacetylase 3 (hdac3) is specifically required for liver development in zebrafish. Dev Biol. 2008;317:336–353
  40. Knutson SK, Chyla BJ, Amann JM, Bhaskara S, Huppert SS, Hiebert SW. Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks. EMBO J. 2008;27:1017–1028
  41. Wang AG, Seo SB, Moon HB, Shin HJ, Kim DH, Kim JM, et al. Hepatic steatosis in transgenic mice overexpressing human histone deacetylase 1. Biochem Biophys Res Commun. 2005;330:461–466
  42. Wang AG, Kim SU, Lee SH, Kim SK, Seo SB, Yu DY, et al. Histone deacetylase 1 contributes to cell cycle and apoptosis. Biol Pharm Bull. 2005;28:1966–1970
  43. Jung M. Inhibitors of histone deacetylase as new anticancer agents. Curr Med Chem. 2001;8:1505–1511
  44. Johnstone RA. The evolution of inaccurate mimics. Nature. 2002;418:524–526
  45. Duvic M, Vu J. Vorinostat: a new oral histone deactylase inhibitor approved for cutaneous T-cell ymphoma. Expert Opin Investig Drugs. 2007;16:1111–1120
  46. Lu YS, Kashida Y, Kulp SK, Wang YC, Wang D, Hung JH, et al. Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma. Hepatology. 2007;46:1119–1130
  47. Herold C, Ganslmayer M, Ocker M, Hermann M, Geerts A, Hahn EG, et al. The histone-deacetylase inhibitor Trichostatin A blocks proliferation and triggers apoptotic programs in hepatoma cells. J Hepatol. 2002;36:233–240
  48. Wakabayashi K, Saito H, Kaneko F, Nakamoto N, Tada S, Hibi T. Gene expression associated with the decrease in malignant phenotype of human liver cancer cells following stimulation with a histone deacetylase inhibitor. Int J Oncol. 2005;26:233–239
  49. Henkens T, Papeleu P, Elaut G, Vinken M, Rogiers V, Vanhaecke T. Trichostatin A, a critical factor to maintain differentiation in primary cultures of rat hepatocytes. Toxicol Appl Pharmacol. 2007;218:64–71
  50. Papeleu P, Wullaert A, Elaut G, Henkens T, Vinken M, Laus G, et al. Inhibition of NF-kappaB activation by the histone deacetylase inhibitor 4-Me2N-BAVAH induces an early G1 cell cycle arrest in primary hepatocytes. Cell Prolif. 2007;40:640–655
  51. Vinken M, Henkens T, Snykers S, Lukaszuk A, Tourwé D, Rogiers V, et al. The novel histone deacetylase inhibitor 4-Me2N-BAVAH differentially affects cell junctions between primary hepatocytes. Toxicology. 2007;236:92–102
  52. Vinken M, Henkens T, Vanhaecke T, Papeleu P, Geerts A, Van Rossen E, et al. Trichostatin A enhances gap junctional intercellular communication in primary cultures of adult rat hepatocytes. Toxicol Sci. 2006;91:484–492
  53. Baylin SB. DNA methylation and gene silencing in cancer. Nat Clin Pract Oncol. 2005;2:4–11
  54. Rice KL, Hormaeche I, Licht JD. Epigenetic regulation of normal and malignant hematopoiesis. Oncogene. 2007;26:6697–6714
  55. Costello JF, Plass C. Methylation matters. J Med Genet. 2001;38:285–303
  56. Métivier R, Gallais R, Tiffoche C, Le Peron C, Jurkowska RZ, Carmouche RP, et al. Cyclical DNA methylation of a transcriptionally active promoter. Nature. 2008;452:45–50
  57. Massillon D, Arinze IJ, Xu C, Bone F. Regulation of glucose-6-phosphatase gene expression in cultured hepatocytes and H4IIE cells by short-chain fatty acids: role of hepatic nuclear factor-4alpha. J Biol Chem. 2003;278:40694–40701
  58. Park HJ, Yu E, Shim YH. DNA methyltransferase expression and DNA hypermethylation in human hepatocellular carcinoma. Cancer Lett. 2006;233:271–278
  59. Pradhan S, Esteve PO. Mammalian DNA (cytosine-5) methyltransferases and their expression. Clin Immunol. 2003;109:6–16
  60. Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet. 2000;9:2395–2402
  61. Kuhlmann M, Borisova BE, Kaller M, Larsson P, Stach D, Na J, et al. Silencing of retrotransposons in Dictyostelium by DNA methylation and RNAi. Nucleic Acids Res. 2005;33:6405–6417
  62. Jurkowski TP, Meusburger M, Phalke S, Helm M, Nellen W, Reuter G, et al. Human DNMT2 methylates tRNAAsp molecules using a DNA methyltransferase-like catalytic mechanism. RNA. 2008;14:1663–1670
  63. Liang G, Chan MF, Tomigahara Y, Tsai YC, Gonzales FA, Li E, et al. Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements. Mol Cell Biol. 2002;22:480–491
  64. Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31:89–97
  65. Suetake I, Shinozaki F, Miyagawa J, Takeshima H, Tajima S. DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. J Biol Chem. 2004;279:27816–27823
  66. Gonzalo S, Jaco I, Fraga MF, Chen T, Li E, Esteller M, et al. DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol. 2006;8:416–424
  67. Turek-plewa J, Jagodzinski PP. The role of mammalian DNA methyltransferases in the regulation of gene expression. Cell Mol Biol Lett. 2005;10:631–647
  68. Qiu W, Zhou B, Zou H, Liu X, Chu PG, Lopez R, et al. Hypermethylation of growth arrest DNA damage-inducible gene 45 beta promotor in human heptocellualr carcinoma. Am J Pathol. 2004;165:1689–1699
  69. Zhu WG, Otterson GA. The interaction of histone deacetylase inhibitors and DNA methyltransferase inhibitors in the treatment of human cancer cells. Curr Med Chem Anticancer Agents. 2003;3:187–199
  70. Laird PW. Cancer epigenetics. Hum Mol Genet. 2005;14:R65–R76
  71. Yoo CB, Cheng JC, Jones PA. Zebularine: a new drug for epigenetic therapy. Biochem Soc Trans. 2004;32:910–912
  72. Stresemann C, Lyko F. Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine. Int J Cancer. 2008;123:8–13
  73. Rogiers V, Vanhaecke T, De Rop E, Fraczek J. Title of invention: stabilisation of the phenotypic properties of isolated primary cells. International patent number: PCT/EP2008/056706.
  74. Lin X, Asgari K, Putzi MJ, Gage WR, Yu X, Cornblatt BS, et al. Reversal of GSTP1 CpG island hypermethylation and reactivation of pi-class glutathione S-transferase (GSTP1) expression in human prostate cancer cells by treatment with procainamide. Cancer Res. 2001;61:8611–8616
  75. Villar-Garea A, Fraga MF, Espada J, Esteller M. Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. Cancer Res. 2003;63:4984–4989
  76. Piña IC, Gautschi JT, Wang GY, Sanders ML, Schmitz FJ, France D, et al. Psammaplins from the sponge Pseudoceratina purpurea: inhibition of both histone deacetylase and DNA methyltransferase. J Org Chem. 2003;68:3866–3873
  77. Belinsky SA, Klinge DM, Stidley CA, Issa JP, Herman JG, March TH, et al. Inhibition of DNA methylation and histone deacetylation prevents murine lung cancer. Cancer Res. 2003;63:7089–7093
  78. Klisovic MI, Maghraby EA, Parthun MR, Guimond M, Sklenar AR, Whitman SP, et al. Depsipeptide (FR 901228) promotes histone acetylation, gene transcription, apoptosis and its activity is enhanced by DNA methyltransferase inhibitors in AML1/ETO-positive leukemic cells. Leukemia. 2003;17:350–358
  79. Brueckner B, Lyko F. DNA methyltransferase inhibitors: old and new drugs for an epigenetic cancer therapy. Trends Pharmacol Sci. 2004;25:551–554
  80. Vanhaecke T, Rogiers V. Hepatocyte cultures in drug metabolism and toxicological research and testing. In: Phillips IR, Shephard EA, editors. Cytochrome P450 Protocols. Methods in molecular biology. 2nd ed. Totowa, NJ: Humana Press Inc.; 2006. p. 209–27.
  81. Elaut G, Henkens T, Papeleu P, Snykers S, Vinken M, Vanhaecke T, et al. Molecular mechanisms underlying the dedifferentiation process of isolated hepatocytes and their cultures. Curr Drug Metab. 2006;7:629–660
  82. Schrem H, Klempnauer J, Borlak J. Liver-enriched transcription factors in liver function and development. Part I: the hepatocyte nuclear factor network and liver-specific gene expression. Pharmacol Rev. 2002;54:129–158
  83. Padgham CR, Boyle CC, Wang XJ, Raleigh SM, Wright MC, Paine AJ. Alteration of transcription factor mRNAs during the isolation and culture of rat hepatocytes suggests the activation of a proliferative mode underlies their de-differentiation. Biochem Biophys Res Commun. 1993;197:599–605
  84. Rodriguez-Antona C, Donato MT, Boobis A, Edwards RJ, Watts PS, Castell JV, et al. Cytochrome P450 expression in human hepatocytes and hepatoma cell lines: molecular mechanisms that determine lower expression in cultured cells. Xenobiotica. 2002;32:505–520
  85. Zaret KS, Watts J, Xu J, Wandzioch E, Smale ST, Sekiya T. Pioneer factors, genetic competence, and inductive signaling: programming liver and pancreas progenitors from the endoderm. Cold Spring Harb Symp Quant Biol. 2008;[ahead of print]
  86. Kistanova E, Dell H, Tsantili P, Falvey E, Cladaras C, Hadzopoulou-Cladaras M. The activation function-1 of hepatocyte nuclear factor-4 is an acidic activator that mediates interactions through bulky hydrophobic residues. Biochem J. 2001;356:635–642
  87. Green VJ, Kokkotou E, Ladias JA. Critical structural elements and multitarget protein interactions of the transcriptional activator AF-1 of hepatocyte nuclear factor 4. J Biol Chem. 1998;273:29950–29957
  88. Wang JC, Stafford JM, Granner DK. SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. J Biol Chem. 1998;273:30847–30850
  89. Sladek FM, Ruse MD, Nepomuceno L, Huang SM, Stallcup MR. Modulation of transcriptional activation and coactivator interaction by a splicing variation in the F domain of nuclear receptor hepatocyte nuclear factor 4alpha1. Mol Cell Biol. 1999;19:6509–6522
  90. Yoshida E, Aratani S, Itou H, Miyagishi M, Takiguchi M, Osumu T, et al. Functional association between CBP and HNF4 in trans-activation. Biochem Biophys Res Commun. 1997;241:664–669
  91. Dell H, Hadzopoulou-Cladaras M. CREB-binding protein is a transcriptional coactivator for hepatocyte nuclear factor-4 and enhances apolipoprotein gene expression. J Biol Chem. 1999;274:9013–9021
  92. Torres-Padilla ME, Sladek FM, Weiss MC. Developmentally regulated N-terminal variants of the nuclear receptor hepatocyte nuclear factor 4alpha mediate multiple interactions through coactivator and corepressor-histone deacetylase complexes. J Biol Chem. 2002;277:44677–44687
  93. Torres-Padilla ME, Weiss MC. Effects of interactions of hepatocyte nuclear factor 4alpha isoforms with coactivators and corepressors are promoter-specific. FEBS Lett. 2003;539:19–23
  94. Martinez-Jimenez CP, Castell JV, Gomez-Lechon MJ, Jover R. Transcriptional activation of CYP2C9, CYP1A1, and CYP1A2 by hepatocyte nuclear factor 4alpha requires coactivators peroxisomal proliferator activated receptor-gamma coactivator 1alpha and steroid receptor coactivator 1. Mol Pharmacol. 2006;70:1681–1692
  95. Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O’Malley B, et al. Activation of PPARgamma coactivator-1 through transcription factor docking. Science. 1999;286:1368–1371
  96. Batsche E, Desroches J, Bilodeau S, Gauthier Y, Drouin J. Rb enhances p160/SRC coactivator-dependent activity of nuclear receptors and hormone responsiveness. J Biol Chem. 2005;280:19746–19756
  97. Ruse MD, Privalsky ML, Sladek FM. Competitive cofactor recruitment by orphan receptor hepatocyte nuclear factor 4alpha1: modulation by the F domain. Mol Cell Biol. 2002;22:1626–1638
  98. Maeda Y, Seidel SD, Wei G, Liu X, Sladek FM. Repression of hepatocyte nuclear factor 4alpha tumor suppressor p53: involvement of the ligand-binding domain and histone deacetylase activity. Mol Endocrinol. 2002;16:402–410
  99. Ban N, Yamada Y, Someya Y, Miyawaki K, Ihara Y, Hosokawa M, et al. Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter. Diabetes. 2002;51:1409–1418
  100. Soutoglou E, Papafotiou G, Katrakili N, Talianidis I. Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins. J Biol Chem. 2000;275:12515–12520
  101. Dohda T, Kaneoka H, Inayoshi Y, Kamihira M, Miyake K, Iijima S. Transcriptional coactivators CBP and p300 cooperatively enhance HNF-1alpha-mediated expression of the albumin gene in hepatocytes. J Biochem. 2004;136:313–319
  102. Soutoglou E, Viollet B, Vaxillaire M, Yaniv M, Pontoglio M, Talianidis I. Transcription factor-dependent regulation of CBP and P/CAF histone acetyltransferase activity. EMBO J. 2001;20:1984–1992
  103. Rausa FM, Tan Y, Costa RH. Association between hepatocyte nuclear factor 6 (HNF-6) and FoxA2 DNA binding domains stimulates FoxA2 transcriptional activity but inhibits HNF-6 DNA binding. Mol Cell Biol. 2003;23:437–449
  104. Yoshida Y, Hughes DE, Rausa FM, Kim IM, Tan Y, Darlington GJ, et al. C/EBPalpha and HNF6 protein complex formation stimulates HNF6-dependent transcription by CBP coactivator recruitment in HepG2 cells. Hepatology. 2006;43:276–286
  105. Erickson RL, Hemati N, Ross SE, MacDougald OA. p300 coactivates the adipogenic transcription factor CCAAT/enhancer-binding protein alpha. J Biol Chem. 2001;276:16348–16355
  106. Chen PL, Riley DJ, Chen Y, Lee WH. Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs. Genes Dev. 1996;10:2794–2804
  107. Charles A, Tang X, Crouch E, Brody JS, Xiao ZX. Retinoblastoma protein complexes with C/EBP proteins and activates C/EBP-mediated transcription. J Cell Biochem. 2001;83:414–425
  108. Chen CJ, Deng Z, Kim AY, Blobel GA, Lieberman PM. Stimulation of CREB binding protein nucleosomal histone acetyltransferase activity by a class of transcriptional activators. Mol Cell Biol. 2001;21:476–487
  109. Mink S, Haenig B, Klempnauer KH. Interaction and functional collaboration of p300 and C/EBPbeta. Mol Cell Biol. 1997;17:6609–6617
  110. Cui TX, Piwien-Pilipuk G, Huo JS, Kaplani J, Kwok R, Schwartz J. Endogenous CCAAT/enhancer binding protein beta and p300 are both regulated by growth hormone to mediate transcriptional activation. Mol Endocrinol. 2005;19:2175–2186
  111. Cesena TI, Cardinaux JR, Kwok R, Schwartz J. CCAAT/enhancer-binding protein (C/EBP) beta is acetylated at multiple lysines: acetylation of C/EBPbeta at lysine 39 modulates its ability to activate transcription. J Biol Chem. 2007;282:956–967
  112. Wiper-Bergeron N, Salem HA, Tomlinson JJ, Wu D, Hache RJ. Glucocorticoid-stimulated preadipocyte differentiation is mediated through acetylation of C/EBPbeta by GCN5. Proc Natl Acad Sci USA. 2007;104:2703–2708
  113. Shim EY, Woodcock C, Zaret KS. Nucleosome positioning by the winged helix transcription factor HNF3. Genes Dev. 1998;12:5–10
  114. Cirillo LA, Lin FR, Cuesta I, Friedman D, Jarnik M, Zaret KS. Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. Mol Cell. 2002;9:279–289
  115. Chaya D, Hayamizu T, Bustin M, Zaret KS. Transcription factor FoxA (HNF3) on a nucleosome at an enhancer complex in liver chromatin. J Biol Chem. 2001;276:44385–44389
  116. Lea MA, Ibeh C, Shah N, Moyer MP. Induction of differentiation of colon cancer cells by combined inhibition of kinases and histone deacetylase. Anticancer Res. 2007;27:741–748
  117. Mayo C, Lloreta J, Real FX, Mayol X. In vitro differentiation of HT-29 M6 mucus-secreting colon cancer cells involves a trychostatin A and p27(KIP1)-inducible transcriptional program of gene expression. J Cell Physiol. 2007;212:42–50
  118. Hinnebusch BF, Meng S, Wu JT, Archer SY, Hodin RA. The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation. J Nutr. 2002;132:1012–1017
  119. Gensert JM, Baranova OV, Weinstein DE, Ratan RR. CD81, a cell cycle regulator, is a novel target for histone deacetylase inhibition in glioma cells. Neurobiol Dis. 2007;26:671–680
  120. Asklund T, Appelskog IB, Ammerpohl O, Ekström TJ, Almqvist PM. Histone deacetylase inhibitor 4-phenylbutyrate modulates glial fibrillary acidic protein and connexin 43 expression, and enhances gap-junction communication, in human glioblastoma cells. Eur J Cancer. 2004;40:1073–1081
  121. Kumagai T, Wakimoto N, Yin D, Gery S, Kawamata N, Takai N, et al. Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (Vorinostat, SAHA) profoundly inhibits the growth of human pancreatic cancer cells. Int J Cancer. 2007;121:656–665
  122. Munster PN, Troso-Sandoval T, Rosen N, Rifkind R, Marks PA, Richon VM. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells. Cancer Res. 2001;61:8492–8497
  123. Emanuele S, Lauricella M, Carlisi D, Vassallo B, D’Anneo A, Di Fazio P, et al. SAHA induces apoptosis in hepatoma cells and synergistically interacts with the proteasome inhibitor Bortezomib. Apoptosis. 2007;12:1327–1338
  124. Armeanu S, Pathil A, Venturelli S, Mascagni P, Weiss TS, Gottlicher M, et al. Apoptosis on hepatoma cells but not on primary hepatocytes by histone deacetylase inhibitors valproate and ITF2357. J Hepatol. 2005;42:210–217
  125. Papeleu P, Vanhaecke T, Elaut G, Vinken M, Henkens T, Snykers S, et al. Differential effects of histone deacetylase inhibitors in tumor and normal cells-what is the toxicological relevance?. Crit Rev Toxicol. 2005;35:363–378
  126. Henkens T, Vinken M, Lukaszuk A, Tourwé D, Vanhaecke T, Rogiers V. Differential effects of hydroxamate histone deacetylase inhibitors on cellular functionality and gap junctions in primary cultures of mitogen-stimulated hepatocytes. Toxicol Lett. 2008;178:37–43
  127. Vanhaecke T, Henkens T, Kass GE, Rogiers V. Effect of the histone deacetylase inhibitor trichostatin A on spontaneous apoptosis in various types of adult rat hepatocyte cultures. Biochem Pharmacol. 2004;68:753–760
  128. Bort R, Gomez-Lechon MJ, Castell JV, Jover R. Role of hepatocyte nuclear factor 3 gamma in the expression of human CYP2C genes. Arch Biochem Biophys. 2004;426:63–72
  129. Rodrı´guez-Antona C, Bort R, Jover R, Tindberg N, Ingelman-Sundberg M, Gómez-Lechón MJ, et al. Transcriptional regulation of human CYP3A4 basal expression by CCAAT enhancer-binding protein alpha and hepatocyte nuclear factor-3 gamma. Mol Pharmacol. 2003;63:1180–1189
  130. Haarmann-Stemmann T, Bothe H, Kohli A, Sydlik U, Abel J, Fritsche E. Analysis of the transcriptional regulation and molecular function of the Aryl Hydrocarbon Receptor Repressor in human cell lines. Drug Metab Dispos. 2007;35:2262–2269
  131. Kim JY, Ahn MR, Kim DK, Sheen YY. Histone deacetylase inhibitor stimulate CYP3A4 proximal promoter activity in HepG2 cells. Arch Pharm Res. 2004;27:407–414
  132. Tronche F, Rollier A, Bach I, Weiss MC, Yaniv M. The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation. Mol Cell Biol. 1989;9:4759–4766
  133. Petropoulos CJ, Yaswen P, Panzica M, Fausto N. Methylation of the alphafetoprotein gene in cell populations isolated from rat livers during carcinogenesis. Nucleic Acids Res. 1985;13:8105–8118
  134. Piechocki MP, Burk RD, Ruch RJ. Regulation of connexin32 and connexin43 gene expression by DNA methylation in rat liver cells. Carcinogenesis. 1999;20:401–406
  135. Vieira I, Sonnier M, Cresteil T. Developmental expression of CYP2E1 in the human liver. Hypermethylation control of gene expression during the neonatal period. Eur J Biochem. 1996;238:476–483
  136. Hammons GJ, Yan-Sanders Y, Jin B, Blann E, Kadlubar FF, Lyn-Cook BD. Specific site methylation in the 5′-flanking region of CYP1A2 interindividual differences in human livers. Life Sci. 2001;69:839–845
  137. Matsunaga E, Gonzalez FJ. Specific cytosine demethylations within the first exons of the rat CYP2D3 and CYP2D5 genes are associated with activation of hepatic gene expression during development. DNA Cell Biol. 1990;9:443–452
  138. Yokomori N, Kobayashi R, Moore R, Sueyoshi T, Nehishi M. A DNA methylation site in the male-specific P450 (Cyp 2d-9) promoter and binding of the heteromeric transcription factor GABP. Mol Cell Biol. 1995;15:5355–5362
  139. Yokomori N, Nishio K, Aida K, Negishi M. Transcriptional regulation by HNF-4 of the steroid 15alpha-hydroxylase P450 (Cyp2a-4) gene in mouse liver. J Steroid Biochem Mol Biol. 1997;62:307–314
  140. Kwon MS, Kim SJ, Lee SY, Jeong JH, Lee ES, Kang HS. Epigenetic silencing of the sulfotransferase 1A1 gene by hypermethylation in breast tissue. Oncol Rep. 2006;15:27–32
  141. Benayahu D, Akavia UD, Shur I. Differentiation of bone marrow stroma-derived mesenchymal cells. Curr Med Chem. 2007;14:173–179
  142. Theise ND. Gastrointestinal stem cells. III. Emergent themes of liver stem cell biology: niche, quiescence, self-renewal, and plasticity. Am J Physiol Gastrointest Liver Physiol. 2006;290:G189–G193
  143. Naveiras O, Daley GQ. Stem cells and their niche: a matter of fate. Cell Mol Life Sci. 2006;63:760–766
  144. Moore KA, Lemischka IR. Stem cells and their niches. Science. 2006;311:1880–1885
  145. Kondo T. Epigenetic alchemy for cell fate conversion. Curr Opin Genet Dev. 2006;16:502–507
  146. Zardo G, Cimino G, Nervi C. Epigenetic plasticity of chromatin in embryonic and hematopoietic stem/progenitor cells: therapeutic potential of cell reprogramming. Leukemia. 2008;22:1503–1518
  147. Song MR, Ghosh A. FGF2-induced chromatin remodeling regulates CNTF-mediated gene expression and astrocyte differentiation. Nat Neurosci. 2004;7:229–235
  148. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–676
  149. Sathananthan AH, Trounson A. Human embryonic stem cells and their spontaneous differentiation. Ital J Anat Embryol. 2005;110:151–157
  150. Lavon N, Benvenisty N. Study of hepatocyte differentiation using embryonic stem cells. J Cell Biochem. 2005;96:1193–1202
  151. Odorico JS, Kaufman DS, Thomson JA. Multilineage differentiation from human embryonic stem cell lines. Stem Cells. 2001;19:193–204
  152. Rambhatla L, Chiu CP, Kundu P, Peng Y, Carpenter MK. Generation of hepatocyte-like cells from human embryonic stem cells. Cell Transplant. 2003;12:1–11
  153. Hay DC, Zhao D, Fletcher J, Hewitt ZA, McLean D, Urruticoechea-Uriguen A, et al. Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo. Stem Cells. 2008;26:894–902
  154. Snykers S, Vanhaecke T, De Becker A, Papeleu P, Vinken M, Van Riet I, et al. Chromatin remodeling: a key-factor in the endogenic differentiation of human mesenchymal stem cells. BMC Dev Biol. 2007;7:1–15
  155. Sgodda M, Aurich H, Kleist S, Aurich I, König S, Dollinger MM, et al. Hepatocyte differentiation of mesenchymal stem cells from rat peritoneal adipose tissue in vitro and in vivo. Exp Cell Res. 2007;313:2875–2886
  156. Yamazaki S, Miki K, Hasegawa K, Sata M, Takayama T, Makuuchi M. Sera from liver failure patients and a demethylating agent stimulate transdifferentiation of murine bone marrow cells into hepatocytes in coculture with nonparenchymal liver cells. J Hepatol. 2003;39:17–23
  157. Kang XQ, Zang WJ, Bao LJ, Li DL, Song TS, Xu XL, et al. Fibroblast growth factor-4 and hepatocyte growth factor induce differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocytes. World J Gastroenterol. 2005;11:7461–7465
  158. Ong SY, Dai H, Leong KW. Hepatic differentiation potential of commercially available human mesenchymal stem cells. Tissue Eng. 2006;12:3477–3485
  159. Kwak DH, Yu K, Kim SM, Lee DH, Kim SM, Jung JU, et al. Dynamic changes of gangliosides expression during the differentiation of embryonic and mesenchymal stem cells into neural cells. Exp Mol Med. 2006;38:668–676
  160. Park KS, Lee YS, Kang KS. In vitro neuronal and osteogenic differentiation of mesenchymal stem cells from human umbilical cord blood. J Vet Sci. 2006;7:343–348
  161. Seo MJ, Suh SY, Bae YC, Jung JS. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun. 2005;328:258–264
  162. Hsieh J, Nakashima K, Kuwabara T, Mejia E, Gage FH. Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells. Proc Natl Acad Sci USA. 2004;101:16659–16664
  163. Illi B, Scopece A, Nanni S, Farsetti A, Morgante L, Biglioli P, et al. Epigenetic histone modification and cardiovascular lineage programming in mouse embryonic stem cells exposed to laminar shear stress. Circ Res. 2005;96:501–508
  164. Kawamura T, Ono K, Morimoto T, Wada H, Hirai M, Hidaka K, et al. Acetylation of GATA-4 is involved in the differentiation of embryonic stem cells into cardiac myocytes. J Biol Chem. 2005;280:19682–19688
  165. Milhem M, Mahmud N, Lavelle D, Araki H, DeSimone J, Saunthararajah Y, et al. Modification of hematopoietic stem cell fate by 5aza 2′deoxycytidine and trichostatin A. Blood. 2004;103:4102–4110
  166. Schmittwolf C, Kirchhof N, Jauch A, Dürr M, Harder F, Zenke M, et al. In vivo haematopoietic activity is induced in neurosphere cells by chromatin-modifying agents. EMBO J. 2005;24:554–566
  167. Yoshida Y, Shimomura T, Sakabe T, Ishii K, Gonda K, Matsuoka S, et al. A role of Wnt/beta-catenin signals in hepatic fate specification of human umbilical cord blood-derived mesenchymal stem cells. Am J Physiol Gastrointest Liver Physiol. 2007;293:G1089–G1098
  168. Stock P, Staege MS, Müller LP, Sgodda M, Völker A, Volkmer I, et al. Hepatocytes derived from adult stem cells. Transplant Proc. 2008;40:620–623
  169. De Kock J, Vanhaecke T, Rogiers V, Snykers S. Chromatin remodelling, a novel strategy to expedite the hepatic differentiation of adult bone marrow stem cells in vitro. AATEX. 2008;14:605–611
  170. Jori FP, Napolitano MA, Melone MA, Cippolaro M, Cascino A, Altucci L, et al. Molecular pathways involved in neural in vitro differentiation of marrow stromal stem cells. J Cell Biochem. 2005;94:645–655
  171. Shen S, Li J, Cassaccia-Bonnefil P. Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain. J Cell Biol. 2005;169:577–589
  172. Enright BP, Sung LY, Chang CC, Yang X, Tian XC. Methylation and acetylation characteristics of cloned bovine embryos from donor cells treated with 5-aza-2′-deoxycytidine. Biol Reprod. 2005;72:944–948
  173. Soto-Gutierrez A, Navarro-Alvarez N, Rivas-Carrillo JD, Chen Y, Yamatsuji T, Tanaka N, et al. Differentiation of human embryonic stem cells to hepatocytes using deleted variant of HGF and poly-amino-urethane-coated nonwoven polytetrafluoroethylene fabric. Cell Transplant. 2006;15:335–341
  174. Mizumoto H, Aoki K, Nakazawa K, Ijima H, Funatsu K, Kajiwara T. Hepatic differentiation of embryonic stem cells in HF/organoid culture. Transplant Proc. 2008;40:611–613
  175. Cascio S, Zaret KS. Hepatocyte differentiation initiates during endodermal-mesenchymal interactions prior to liver formation. Development. 1991;113:217–225
  176. Shiojiri N. Enzymo- and immunocytochemical analyses of the differentiation of liver cells in the prenatal mouse. J Embryol Exp Morphol. 1981;62:139–152
  177. Kmiec Z. Cooperation of liver cells in health and disease. Adv Anat Embryol Cell Biol. 2001;161:1–151
  178. Rozga J. Liver support technology–an update. Xenotransplantation. 2006;13:380–389
  179. Pearson H. Stem-cell tagging shows flaws. Nature. 2006;439:519
  180. Brulport M, Schormann W, Bauer A, Hermes M, Elsner C, Hammersen FJ, et al. Fate of extrahepatic human stem and precursor cells after transplantation into mouse livers. Hepatology. 2007;46:861–870
  181. Hengstler JG, Brulport M, Schormann W, Bauer A, Hermes M, Nussler AK, et al. Generation of human hepatocytes by stem cell technology: definition of the hepatocyte. Expert Opin Drug Metab Toxicol. 2005;1:61–74
  182. Zhou QJ, Xiang LX, Shao JZ, Hu RZ, Lu YL, Yao H, et al. In vitro differentiation of hepatic progenitor cells from mouse embryonic stem cells induced by sodium butyrate. J Cell Biochem. 2007;100:29–42
  183. Sharma NS, Shikhanovich R, Schloss R, Yarmush ML. Sodium butyrate-treated embryonic stem cells yield hepatocyte-like cells expressing a glycolytic phenotype. Biotechnol Bioeng. 2006;94:1053–1063
  184. Li L, Sharma N, Chippada U, Jiang X, Schloss R, Yarmush ML, et al. Functional modulation of ES-derived hepatocyte lineage cells via substrate compliance alteration. Ann Biomed Eng. 2008;36:865–876
  185. Aurich I, Mueller LP, Aurich H, Luetzkendorf J, Tisljar K, Dollinger MM, et al. Functional integration of human mesenchymal stem cell-derived hepatocytes into mouse livers. Gut. 2007;56:405–415
  186. Nakajima M, Iwanari M, Yokoi T. Effects of histone deacetylation and DNA methylation on the constitutive and TCDD-inducible expressions of the human CYP1 family in MCF-7 and HeLa cells. Toxicol Lett. 2003;144:247–256
  187. Hooven LA, Mahadevan B, Keshava C, Johns C, Pereira C, Desai D, et al. Effects of suberoylanilide hydroxamic acid and trichostatin A on induction of cytochrome P450 enzymes and benzo[a]pyrene DNA adduct formation in human cells. Bioorg Med Chem Lett. 2005;15:1283–1287
  188. Jin B, Ryu DY. Regulation of CYP1A2 by histone deacetylase inhibitors in mouse hepatocytes. J Biochem Mol Toxicol. 2004;18:131–132
  189. Shehin SE, Stephenson RO, Greenlee WF. Transcriptional regulation of the human CYP1B1 gene. Evidence for involvement of an aryl hydrocarbon receptor response element in constitutive expression. J Biol Chem. 2000;275:6770–6776
  190. Rogiers V, Akrawi M, Vercruysse A, Phillips IR, Shephard EA. Effects of the anticonvulsant, valproate, on the expression of components of the cytochrome-P-450-mediated monooxygenase system and glutathione S-transferases. Eur J Biochem. 1995;231:337–343
  191. Dannenberg LO, Chen HJ, Tian H, Edenberg HJ. Differential regulation of the alcohol dehydrogenase 1B (ADH1B) and ADH1C genes by DNA methylation and histone deacetylation. Alcohol Clin Exp Res. 2006;30:928–937
  192. Klick DE, Shadley JD, Hines RN. Differential regulation of human hepatic flavin containing monooxygenase 3 (FMO3) by CCAAT/enhancer-binding protein beta (C/EBPbeta) liver inhibitory and liver activating proteins. Biochem Pharmacol. 2008;76:268–278
  193. Bakker J, Lin X, Nelson WG. Methyl-CpG binding domain protein 2 represses transcription from hypermethylated pi-class glutathione S-transferase gene promoters in hepatocellular carcinoma cells. J Biol Chem. 2002;277:22573–22580
  194. Ebert MN, Klinder A, Peters WH, Schäferhenrich A, Sendt W, Scheele J, et al. Expression of glutathione S-transferases (GSTs) in human colon cells and inducibility of GSTM2 by butyrate. Carcinogenesis. 2003;24:1637–1644
  195. Pool-Zobel BL, Selvaraju V, Sauer J, Kautenburger T, Kiefer J, Richter KK, et al. Butyrate may enhance toxicological defence in primary, adenoma and tumor human colon cells by favourably modulating expression of glutathione S-transferases genes, an approach in nutrigenomics. Carcinogenesis. 2005;26:1064–1076
  196. Schroeder TM, Nair AK, Staggs R, Lamblin AF, Westendorf JJ. Gene profile analysis of osteoblast genes differentially regulated by histone deacetylase inhibitors. BMC Genomics. 2007;8:362
  197. Valentini A, Biancolella M, Amati F, Gravina P, Miano R, Chillemi G, et al. Valproic acid induces neuroendocrine differentiation and UGT2B7 up-regulation in human prostate carcinoma cell line. Drug Metab Dispos. 2007;35:968–972
  198. Lee YC, Higashi Y, Luu C, Shimizu C, Strott CA. Sp1 elements in SULT2B1b promoter and 5′-untranslated region of mRNA: Sp1/Sp2 induction and augmentation by histone deacetylase inhibition. FEBS Lett. 2005;579:3639–3645
  199. Yamashita Y, Shimada M, Harimoto N, Tanaka S, Shirabe K, Ijima H, et al. cDNA microarray analysis in hepatocyte differentiation in Huh7 cells. Cell Transplant. 2004;13:793–799
  200. Khan Z, Akhtar M, Asklund T, Juliusson B, Almqvist PM, Ekström TJ. HDAC inhibition amplifies gap junction communication in neural progenitors: potential for cell-mediated enzyme prodrug therapy. Exp Cell Res. 2007;313:2958–2967
  201. Hattori Y, Fukushima M, Maitani Y. Non-viral delivery of the connexin 43 gene with histone deacetylase inhibitor to human nasopharyngeal tumor cells enhances gene expression and inhibits in vivo tumor growth. Int J Oncol. 2007;30:1427–1439
  202. Hernandez M, Shao Q, Yang XJ, Luh SP, Kandouz M, Batist G, et al. A histone deacetylation-dependent mechanism for transcriptional repression of the gap junction gene cx43 in prostate cancer cells. Prostate. 2006;66:1151–1161
  203. Ogawa T, Hayashi T, Tokunou M, Nakachi K, Trosko JE, Chang CC, et al. Suberoylanilide hydroxamic acid enhances gap junctional intercellular communication via acetylation of histone containing connexin 43 gene locus. Cancer Res. 2005;65:9771–9778
  204. Ammerpohl O, Thormeyer D, Khan Z, Appelskog IB, Gojkovic Z, Almqvist PM, et al. HDACi phenylbutyrate increases bystander killing of HSV-tk transfected glioma cells. Biochem Biophys Res Commun. 2004;324:8–14
  205. Robe PA, Jolois O, N’Guyen M, Princen F, Malgrange B, Merville MP, et al. Modulation of the HSV-TK/ganciclovir bystander effect by n-butyrate in glioblastoma: correlation with gap-junction intercellular communication. Int J Oncol. 2004;25:187–192
  206. Desilets A, Gheorghiu I, Yu SJ, Seidman EG, Asselin C. Inhibition by deacetylase inhibitors of IL-1-dependent induction of haptoglobin involves CCAAT/Enhancer-binding protein isoforms in intestinal epithelial cells. Biochem Biophys Res Commun. 2000;276:673–679
  207. Xu J, Hershman JM. Histone deacetylase inhibitor depsipeptide represses nicotinamide N-methyltransferase and hepatocyte nuclear factor-1beta gene expression in human papillary thyroid cancer cells. Thyroid. 2006;16:151–160
  208. Jin B, Park DW, Nam KW, Oh GT, Lee YS, Ryu DY. CpG methylation of the mouse CYP1A2 promoter. Toxicol Lett. 2004;152:11–18
  209. Hirai A, Yano T, Nishikawa K, Suzuki K, Asano R, Satoh H, et al. Down-regulation of connexin 32 gene expression through DNA methylation in a human renal cell carcinoma cell. Am J Nephrol. 2003;23:172–177
  210. Hagiwara H, Sato H, Ohde Y, Takano Y, Seki T, Ariga T, et al. 5-Aza-2′-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene. Br J Pharmacol. 2008;153:1373–1381
  211. Tan LW, Bianco T, Dobrovic A. Variable promoter region CpG island methylation of the putative tumor suppressor gene Connexin 26 in breast cancer. Carcinogenesis. 2002;23:231–236
  212. Singal R, Tu ZJ, Vanwert JM, Ginder GD, Kiang DT. Modulation of the connexin26 tumor suppressor gene expression through methylation in human mammary epithelial cell lines. Anticancer Res. 2000;20:59–64
  213. Chen Y, Hühn D, Knösel T, Pacyna-Gengelbach M, Deutschmann N, Peterson I. Downregulation of connexin 26 in human lung cancer is related to promoter methylation. Int J Cancer. 2005;113:14–21
  214. Loncarek J, Yamasaki H, Levillain P, Milinkevitch S, Mesnil M. The expression of the tumor suppressor gene connexin 26 is not mediated by methylation in human esophageial cancer cells. Mol Carcinog. 2003;36:74–81
  215. King TJ, Fukushima LH, Donlon TA, Hieber AD, Shimabukuro KA, Bertram JS. Correlation between growth control, neoplastic potential and endogenous connexin43 expression in HeLa cell lines: implications for tumor progression. Carcinogenesis. 2000;21:311–315
  216. Yi Zc, Wang H, Zhang GY, Xia B. Downregulation of connexin 43 in nasopharyngeal carcinoma cells is related to promoter methylation. Oral Oncol. 2007;43:898–904
  217. Jin B, Seong JK, Ryu DY. Tissue-specific and de novo promoter methylation of the mouse glucose transporter 2. Biol Pharm Bull. 2005;28:2054–2057
  218. Cho HH, Park HT, Kim YJ, Bae YC, Suh KT, Jung JS. Induction of osteogenic differentiation of human mesenchymal stem cells by histone deacetylase inhibitors. J Cell Biochem. 2005;96:533–542
  219. Rössig L, Urbich C, Brühl T, Dernbach E, Heeschen C, Chavakis E, et al. Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells. J Exp Med. 2005;201:1825–1835
  220. Lee JH, Hart SR, Skalnik DG. Histone deacetylase activity is required for embryonic stem cell differentiation. Genesis. 2004;38:32–38
  221. Lagace DC, Nachtigal MW. Inhibition of histone deacetylase activity by valproic acid blocks adipogenesis. J Biol Chem. 2004;279:18851–18860
  222. Terranova R, Sauer S, Merkenschlager M, Fisher AG. The reorganisation of constitutive heterochromatin in differentiating muscle requires HDAC activity. Exp Cell Res. 2005;310:344–356
  223. Marin-Husstege M, Muggironi M, Liu A, Casaccia-Bonnefil P. Histone deacetylase activity is necessary for oligodendrocyte lineage progression. J Neurosci. 2002;22:10333–10345

☆ The authors who have taken part in this study declared that they do not have anything to disclose regarding funding from industry or conflict of interest with respect to this manuscript.

PII: S0168-8278(09)00171-8

doi: 10.1016/j.jhep.2009.03.009

Journal of Hepatology
Volume 51, Issue 1 , Pages 187-211 , July 2009

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