Histone-deacetylase inhibitors: Novel drugs for the treatment of cancer

Nature Reviews Drug Discovery

Volumn 1, Issue 4, 2002, Pages 287-299

  Johnstone, Ricky W ^a  

^a PETER MACCALLUM CANCER CENTRE   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICONVULSIVE AGENT; ANTINEOPLASTIC AGENT; APICIDIN; ARGININE DERIVATIVE; ARYLBUTYRIC ACID DERIVATIVE; AZACITIDINE; BENZAMIDE DERIVATIVE; CINNAMIC ACID DERIVATIVE; CYCLIN DEPENDENT KINASE INHIBITOR; DEPSIPEPTIDE; DEXAMETHASONE; FLUOROURACIL; FR 901228; GANCICLOVIR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HISTONE ACETYLTRANSFERASE; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; HYDROXAMIC ACID DERIVATIVE; INDOMETACIN; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; OXAMFLATIN; PHENYLACETIC ACID; REACTIVE OXYGEN METABOLITE; RETINOIC ACID; SHORT CHAIN FATTY ACID; TRICHOSTATIN A; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID; VORINOSTAT; ENZYME INHIBITOR; HISTONE;

ANTINEOPLASTIC ACTIVITY; CANCER GROWTH; CANCER INHIBITION; CHROMATIN STRUCTURE; CLINICAL TRIAL; DNA METHYLATION; DOSE RESPONSE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SPECIFICITY; DYSPEPSIA; ENZYME BINDING; ENZYME INHIBITION; FATIGUE; GENE ACTIVATION; GENE EXPRESSION; GENE MUTATION; GENE TARGETING; GENETIC CODE; GENETIC TRANSCRIPTION; HEMATOLOGIC MALIGNANCY; HUMAN; HYPERURICEMIA; HYPOCALCEMIA; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PLASMA HALF LIFE; PRIORITY JOURNAL; REVIEW; SOMNOLENCE; ACETYLATION; ANIMAL; APOPTOSIS; CELL DIFFERENTIATION; CHROMATIN; DRUG ANTAGONISM; DRUG EFFECT; GENE EXPRESSION REGULATION; METABOLISM; NEOPLASM;

ACETYLATION; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL DIFFERENTIATION; CHROMATIN; CLINICAL TRIALS; DNA METHYLATION; ENZYME INHIBITORS; GENE EXPRESSION REGULATION, NEOPLASTIC; HISTONE DEACETYLASES; HISTONES; HUMANS; NEOPLASMS;

EID: 0036527775     PISSN: 14741776     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrd772     Document Type: Review

References (118)

1. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57-70 (2000).
2. Jacobson, S. & Pillus, L. Modifying chromatin and concepts of cancer. Curr. Opin. Genet. Dev. 9, 175-184 (1999).
3. Wu, J. & Grunstein, M. 25 Years after the nucleosome model: chromatin modifications. Trends Biochem. Sci. 25, 619-623 (2000).
4. Luger, K., Mader, A. W., Richmond, R. K., Sargent, D. F. & Richmond, T. J. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389, 251-260 (1998).
5. Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074-1080 (2001).
6. Flaus, A. & Owen-Hughes, T. Mechanisms for ATP-dependent chromatin remodelling. Curr. Opin. Genet. Dev. 11, 148-154 (2001).
7. Marmorstein, R. & Roth, S. Y. Histone acetyltransferases: function, structure, and catalysis, Curr. Opin. Genet. Dev. 11, 155-161 (2001).
8. Sterner, D. E. & Berger, S. L. Acetylation of histones and transcription-related factors. Microbiol. Mol. Biol. Rev. 64, 435-459 (2000).
9. Gray, S. G. & Ekstrom, T. J. The human histone deacetylase family. Exp. Cell Res. 262, 75-83 (2001).
10. Khochbin, S., Verdel, A., Lemercier, C. & Seigneurin-Berny, D. Functional significance of histone deacetylase diversity. Curr. Opin. Genet Dev. 11, 162-166 (2001).
11. Fischle, W., Kiermer V., Dequiedt, F. & Verdin, E. The emerging role of class II histone deacetylases. Biochem. Cell Biol. 79, 337-348 (2001).
12. Lee, H. J., Chun, M. & Kandror, K. V. Tip60 and HDAC7 interact with the endothelin receptor A and may be involved in downstream signaling. J. Biol. Chem. 276, 16597-16600 (2001).
13. Imai, S., Armstrong, C. M., Kaeberlein, M. & Guarente, L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403, 795-800 (2000).
14. Luo, J. et al. Negative control of p53 by Sir2α promotes cell survival under stress. Cell 107, 137-148 (2001).
15. Vaziri, H. et al. hSIR2(SIRT1) Functions as an NAD-dependent p53 deacetylase. Cell 107, 149-159 (2001).
16. Robertson, K. D. DNA methylation, methyltransferases, and cancer. Oncogene 20, 3139-3155 (2001).
17. Esteller, M. & Herman, J. G. Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J. Pathol. 196, 1-7 (2002)
18. Kouzarides, T. Histone acetylases and deacetylases in cell proliferation. Curr. Opin. Genet. Dev. 9, 40-48 (1999).
19. Muller, C. & Leutz, A. Chromatin remodeling in development and differentiation. Curr. Opin. Genet. Dev. 11, 167-174 (2001).
20. Muraoka, M. et al. p300 Gene alterations in colorectal and gastric carcinomas. Oncogene 12, 1565-1569 (1996).
21. Giles, R. H., Peters, D. J. & Breuning, M. H. Conjunction dysfunction: CBP/p300 in human disease. Trends Genet. 14, 178-183 (1998).
22. Gayther, S. A. et al. Mutations truncating the EP300 acetylase in human cancers. Nature Genet. 24, 300-303 (2000).
23. Goodman, R. H. & Smolik, S. CBP/p300 in cell growth, transformation, and development. Genes Dev. 14, 1553-1577 (2000).
24. Grossman, S. R. p300/CBP/p53 Interaction and regulation of the p53 response. Eur. J. Biochem. 268, 2773-2778 (2001).
25. Liang, J., Prouty, L., Williams, B. J., Dayton, M. A. & Blanchard, K. L. Acute mixed lineage leukemia with an inv(8)(p11g13) resulting in fusion of the genes for MOZ and TIF2. Blood 92, 2118-2122 (1998).
26. Panagopoulos, I. et al. Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10; 16)(q22;p13). Hum. Mol. Genet. 10, 395-404 (2001).
27. Lin, R. J., Sternsdorf, T., Tini, M. & Evans, R. M. Transcriptional regulation in acute promyelocytic leukemia. Oncogene 20, 7204-7215 (2001).
28. Zelent, A., Guidez, F., Melnick, A., Waxman, S. & Licht, J. D. Translocations of the RARα gene in acute promyelocytic leukemia. Oncogene 20, 7186-7203 (2001).
29. Pandolfi, P. P. Transcription therapy for cancer. Oncogene 20, 3116-3127 (2001).
30. Heibert, S. W. et al. Mechanisms of transcriptional repression by the t(8;21)-, t(12:21)-, and inv(16)-encoded fusion proteins. Cancer Chemother. Pharmacol. 48, S31-S34 (2001).
31. Licht, J. D. AML1 and the AML1-ETO fusion protein in the pathogenesis of t(8;21) AML. Oncogene 20, 5660-5679 (2001).
32. Huynh, K. D., Fischle, W., Verdin, E. & Bardwell, V. J. BCoR, A novel corepressor involved in BCL-6 repression. Genes Dev. 14, 1810-1823 (2000).
33. McKinsey, T. A., Zhang, C. L. & Olson, E. N. Control of muscle development by dueling HATs and HDACs. Curr. Opin. Genet. Dev. 11, 497-504 (2001).
34. Soengas, M. S. et al. Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature 409, 207-211 (2001).
35. Teitz, T. et al. Caspase -8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nature Med. 6, 529-535 (2000).
36. Rountree, M. R., Bachman, K. E., Herman, J. G. & Baylin, S. B. DNA methylation, chromatin inheritance, and cancer. Oncogene 20, 3156-3165 (2001).
37. Dervan, P. B. & Burli, R. W. Sequence-specific DNA recognition by polyamides. Curr. Opin. Chem. Biol. 3, 688-693 (1999).
38. Mapp, A. K., Ansari, A. Z., Ptashne, M. & Dervan, P. B. Activation of gene expression by small molecule transcription factors. Proc. NatlAcad. Sci. USA 97, 3930-3935 (2000).
39. Liu, P. Q. et al. Regulation of an endogenous locus using a panel of designed zinc finger proteins targeted to accessible chromatin regions. Activation of vascular endothelial growth factor A. J. Biol. Chem. 276, 11323-11334 (2001).
40. Finnin, M. S. et al. Structures of a histone deacetylase homologue bound to the TSA and SARA inhibitors. Nature 401, 188-193 (1999).
41. Marks, P. A., Richon, V. M., Breslow, R. & Rifkind, R. A. Histone deacetylase inhibitors as new cancer drugs. Curr. Opin. Oncol. 13, 477-483 (2001).
42. Weidle, U. H. & Grossmann, A. Inhibition of histone deacetylases: a new strategy to target epigenetic modifications for anticancer treatment. Anticancer Res. 20, 1471-1485 (2000).
43. Phiel, C. J. et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J. Biol. Chem. 76, 36734-36741 (2001).
44. Gottlicher, M. et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J. 20, 6969-6978 (2001).
45. Komatsu, Y. et al. Cyclic hydroxamic-acid-containing peptide 31, a potent synthetic histone deacetylase inhibitor with antitumor activity. Cancer Res. 61, 4459-4466 (2001).
46. Furumai, R. et al. Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. Proc. Natl Acad. Sci. USA 98, 87-92 (2001).
47. Mariadason, J. M., Corner, G. A. & Augenlicht, L. H. Genetic reprogramming in pathways of colonic cell maturation induced by short chain fatty acids: comparison with trichostatin A, sulindac, and curcumin and implications for chemoprevention of colon cancer. Cancer Res. 60, 4561-4572 (2000).
48. Zhang, Y. & Reinberg, D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. 15, 2343-2360 (2001).
49. Cameron, E. E., Bachman, K. E., Myohanen, S., Herman, J. G. & Baylin, S. B. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nature Genet. 21, 103-107 (1999).
50. Marks, P. A., Richon, V. M. & Rifkind, R. A. Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J. Natl Cancer Inst. 92, 1210-1216 (2000).
51. Marks, P.A. et al. Histone deacetylases and cancer: causes and therapies. Nature Rev. Cancer 1, 194-202 (2001)
52. Kramer, O. H., Gottlicher, M. & Henzel, T. Histone deacetylase as a therapeutic target. Trends Endocrinol. Metab. 12, 294-300 (2001).
53. Qiu, L. et al. Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells. Mol. Biol. Cell. 11, 2069-2083 (2000).
54. Ruefli, A. A. et al. The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of BID and production of reactive oxygen species. Proc. Natl Acad. Sci. USA 98, 10833-10838 (2001).
55. He, L. Z. et al. Histone deacetylase inhibitors induce remission in transgenic models of therapy-resistant acute promyelocytic leukemia. J. Clin. Invest. 108, 1321-1330 (2001).
56. Ferrara, F. F. et al. Histone deacetylase-targeted treatment restores retinoic acid signaling and differentiation in acute myeloid leukemia. Cancer Res. 61, 2-7 (2001).
57. Kosugi, H. et al. Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia: a new approach to anti-leukemia therapy. Leukemia 13, 1316-1324 (1999).
58. Lipinski, M. M. & Jacks, T. The retinoblastoma gene family in differentiation and development. Oncogene 18, 7873-7882 (1999).
59. Sandor, V. et al. p21-Dependent G1 arrest with downregulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228. Br. J. Cancer 83, 817-825 (2000).
60. WAF1/CIP1/MDA6 in promoting differentiation and preventing mitochondrial dysfunction and apoptosis induced by sodium butyrate in human myelomonocytic leukemia cells (U937). Int. J. Oncol. 19, 181-191 (2001).
61. Burgess, A. J. et al. Up-regulation of p21 (WAF1/CIP1) by histone deacetylase inhibitors reduces their cytotoxicity Mol. Pharmacol. 60, 828-837 (2001).
62. CIP1, but independent of p53. Oncogene 18, 7016-7025 (1999 ).
63. Zhu, L. & Skoultchi, A. I. Coordinating cell proliferation and differentiation. Curr. Opin. Genet. Dev. 11, 91-97 (2001).
64. Munster, P. N. et al. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells. Cancer Res. 61, 8492-8497 (2001).
65. Kwon, S. H. et al. Apicidin, a histone deacetylase inhibitor, induces apoptosis and FAS/FAS ligand expression in human acute promyelocytic leukemia cells. J. Biol. Chem. 6, 6 (2001)
66. Glick, R. D. et al. Hybrid polar histone deacetylase inhibitor induces apoptosis and CD95/CD95 ligand expression in human neuroblastoma. Cancer Res. 59, 4392-4399 (1999).
67. Mello, J. A. & Almouzni, G. The ins and outs of nucleosome assembly. Curr. Opin. Genet. Dev. 11, 136-141 (2001).
68. Green, D. R. Apoptotic pathways: paper wraps stone blunts scissors. Cell 102, 1-4 (2000).
69. Bonnotte, B. et al. Cancer cell sensitization to Fas-mediated apoptosis by sodium butyrate. Cell Death Differ. 5, 480-487 (1998).
70. Bernhard, D. et al. Inhibition of histone deacetylase activity enhances Fas receptor-mediated apoptosis in leukemic lymphoblasts. Cell Death Differ. 8, 1014-1021 (2001).
71. Wang, R., Brunner, T., Zhang, L. & Shi, Y. Fungal metabolite FR901228 inhibits c-Myc and Fas ligand expression. Oncogene 17, 1503-1508 (1998).
72. Bernhard, D. et al. Apoptosis induced by the histone deacetylase inhibitor sodium butyrate in human leukemic lymphoblasts. FASEB J. 13, 1991-2001 (1999).
73. Suzuki, T. et al. Effect of trichostatin A on cell growth and expression of cell cycle- and apoptosis-related molecules in human gastric and oral carcinoma cell lines. Int. J. Cancer 88, 992-997 (2000).
74. L gene expression leads to apoptotic cell death in mesothelioma. Am. J. Respir. Cell. Mol. Biol. 25, 562-568 (2001).
75. Zhu, W. G., Lakshmanan, R. R., Beal, M. D. & Otterson, G. A. DNA methyltransferase inhibition enhances apoptosis induced by histone deacetylase inhibitors. Cancer Res. 61, 1327-1333 (2001).
76. Weiser, T. S. et al. Sequential 5-aza-2′-deoxycytidine-depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO1. J. Immunother. 24, 151-161 (2001).
77. Amin, H. M., Saeed, S. & Alkan, S. Histone deacetylase inhibitors induce caspase-dependent apoptosis and downregulation of DAXX in acute promyelocytic leukaemia with t(15;17). Br. J. Haematol. 115, 287-297 (2001)
78. Trapani, J. A. et al. Perforin-dependent nuclear entry of granzyme B precedes apoptosis, and is not a consequence of nuclear membrane dysfunction. Cell Death Differ. 5, 488-496 (1998).
79. Maeda, T., Towatari, M., Kosugi, H. &Saito, H. Up-regulation of costimulatory/adhesion molecules by histone deacetylase inhibitors in acute myeloid leukemia cells. Blood 96, 3847-3856 (2000).
80. Magner, W. J. et al. Activation of MHC class I, II, and CD40 gene expression by histone deacetylase inhibitors. J. Immunol. 165, 7017-7024 (2000).
81. Mishra, N., Brown, D. R., Olorenshaw, I. M. & Kammer, G. M. Trichostatin A reverses skewed expression of CD154, interieukin-10, and interferon-γ gene and protein expression in lupus T cells. Proc. Natl Acad. Sci. USA 98, 2628-2633 (2001).
82. Shestakova. E., Bandu, M. T., Doly, J & Bonnefoy, E. Inhibition of histone deacetylation induces constitutive derepression of the beta interferon promoter and confers antiviral activity. J. Virol. 75, 3444-3452 (2001).
83. Kim, M. S. et al. Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nature Med. 7, 437-443 (2001).
84. Sternson, S. M., Wong, J. C., Grozinger, C. M. & Schreiber, S. L. Synthesis of 7,200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin. Org. Lett. 3, 4239-4242 (2001).
85. Meinke, P. T. & Liberator, P. Histone deacetylase: a target for antiproliferative and antiprotozoal agents. Curr. Med. Chem. 8, 211-235 (2001).
86. Jung, M. Inhibitors of histone deacetylase as new anticancer agents. Curr. Med. Chem. 8, 1505-1511 (2001).
87. Remiszewski, S. W. et al. Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates. J. Med. Chem. 45, 753-757 (2002).
88. Richon, V. M. et al. A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc. Natl Acad. Sci. USA 95, 3003-3007 (1998).
89. Butler, L. M. et al. Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. Cancer Res. 60, 5165-5170 (2000).
90. Reed, J. C. Dysregulation of apoptosis in cancer. J. Clin. Oncol. 17, 2941-2953 (1999).
91. Takakura, M. et al. Telomerase activation by histone deacetylase inhibitor in normal cells. Nucleic Acids Res. 29, 3006-3011 (2001).
92. Cress, W. D. & Seto, E. Histone deacetylases, transcriptional control, and cancer. J. Cell. Physiol. 184, 1-16 (2000).
93. Terao, Y. et al. Sodium butyrate induces growth arrest and senescence-like phenotypes in gynecologic cancer cells. Int. J. Cancer 94, 257-267 (2001).
94. Vigushin, D. M. et al. Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo. Clin. Cancer Res. 7, 971-976 (2001).
95. Coffey, D. C. et al. The histone deacetylase inhibitor, CBHA, inhibits growth of human neuroblastoma xenografts in vivo, alone and synergistically with all-trans retinoic acid. Cancer Res. 61, 3591-3594 (2001).
96. Ueda, H. et al. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968.III. Antitumor activities on experimental tumors in mice. J. Antibiot. (Tokyo) 47, 315-323 (1994).
97. Saito, A. et al. A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc. Natl Acad. Sci. USA 96, 4592-4597 (1999).
98. Kosugi, H. et al. In vivo effects of a histone deacetylase inhibitor, FK228, on human acute promyelocytic leukemia in NOD/SHI-SCID/SCID mice. Jpn J. Cancer Res. 92, 529-536 (2001).
99. Gilbert, J. et al. A Phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies. Clin. Cancer Res. 7, 2292-2300 (2001).
100. Carducci, M. A. et al. A Phase I clinical and pharmacological evaluation of sodium phenylbutyrate on an 120-hr infusion schedule. Clin. Cancer Res. 7, 3047-3055 (2001).
101. Warrell, R. P. Jr, He, L. Z., Richon, V., Calleja, E. & Pandolfi, P. P. Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. J. Natl Cancer Inst. 90, 1621-1625 (1998).
102. Piekarz, R. L. et al. Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T cell lymphoma: a case report. Blood 98, 2865-2868 (2001).
103. Ruefli, A. A. Suberoylanilide hydroxamic acid (SAHA) overcomes multidrug resistance and induces cell death in P-gp expressing cells. Int. J. Cancer. (in the press)
104. Greenberg, V. L., Williams, J. M., Cogswell, J. P., Mendenhall, M. & Zimmer, S. G. Histone deacetylase inhibitors promote apoptosis and differential cell cycle arrest in anaplastic thyroid cancer cells. Thyroid 11, 315-325 (2001).
105. Harbour, J. W. & Dean, D. C. Chromatin remodeling and Rb activity. Curr. Opin. Cell. Biol. 12, 685-689 (2000).
106. Puri, P. L. et al. Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis. Mol. Cell 8, 885-897 (2001).
107. Kihara-Negishi, F. et al. In vivo complex formation of PU.1 with HDAC1 associated with PU.1-mediated transcriptional repression. Oncogene 20, 6039-6047 (2001).
108. Ashburner, B. P., Westerheide, S. D. & Baldwin, A. S. Jr. The p65 (ReIA) subunit of NF-κB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression. Mol. Cell. Biol. 21, 7065-7077 (2001).
109. Fulks, F., Burgers, W. A., Godin, N., Kasai, M. & Kouzarides, T. DNMT3A binds deacetylases and is recruited by a sequence-specific repressor to silence transcinotion. EMBO J. 20, 2536-2544 (2001).
110. Chen, L., Fischle, W., Verdin, E. & Greene, W. C. Duration of nuclear NF-κB action regulated by reversible acetylation. Science 293, 1653-1657 (2001).
111. Rountree, M. H., Bachman, K. E. & Baylin, S. B. DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nature Genet. 25, 269-277 (2000).
112. Yarden, R. I. & Brody, L. C. BRCA1 interacts with components of the histone deacetylase complex. Proc. Natl Acad. Sci. USA 96, 4983-4988 (1999).
113. Doetzlhoter, A. et al. Histone deacetylase 1 can repress transcription by binding to Sp1. Mol. Cell. Biol. 19, 5504-5511 (1999).
114. Ng, H. H. et al. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nature Genet. 23, 58-61 (1999).
115. Coull, J. J. et al. The human factors YY1 and LSF repress the human immunodeficiency virus type 1 long terminal repeat via recruitment of histone deacetylase 1. J. Virol. 74, 6790-6799 (2000).
116. Robertson, K. D. et al. DNMT1 forms a complex with RB, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nature Genet. 25, 338-342 (2000).
117. Luo, J., Su, F., Chen, D., Shiloh, A. & Gu, W. Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 408, 377-381 (2000).
118. Kim, G. D. et al. Sensing of ionizing radiation-induced DNA damage by ATM through interaction with histone deacetylase. J. Biol. Chem. 274, 31127-31130 (1999).