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Gene Review

HDAC1  -  histone deacetylase 1

Homo sapiens

Synonyms: GON-10, HD1, Histone deacetylase 1, RPD3, RPD3L1
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Disease relevance of HDAC1


Psychiatry related information on HDAC1


High impact information on HDAC1


Chemical compound and disease context of HDAC1


Biological context of HDAC1


Anatomical context of HDAC1

  • These results provide for a model which postulates that MyoD may be co-dependent on HDAC1 and P/CAF for temporally controlling its transcriptional activity before and after the differentiation of muscle cells [26].
  • Coimmunoprecipitation experiments with Swiss 3T3 fibroblasts and 293 cells demonstrate that Sp1 and HDAC1 can be part of the same complex [27].
  • Silencing of Gfi1 expression in myeloid cells reverses G9a and HDAC1 recruitment to p21Cip/WAF1 and elevates its expression [28].
  • In cultured cells, HDAC1/p130 overexpression inhibited activity of the cdc25A promoter through an E2F site [29].
  • We further showed that Sp1 bound to the endogenous eNOS promoter and associated with HDAC1 in non-endothelial HeLa cells [30].

Associations of HDAC1 with chemical compounds

  • Additionally, mutation of the YY1 binding site prevented repression of the promoter by HDAC1 and partially prevented activation of the promoter by trichostatin A [31].
  • Direct interaction of RIP140 with HDAC1 and HDAC3 occurs in vitro and in vivo as demonstrated in co-immunoprecipitation and glutathione S-transferase pull-down experiments [32].
  • Human HDAC1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, Ser(421) and Ser(423), were unambiguously identified [33].
  • HDAC1 was undetectable in MCF-7 cells 30 min after addition of quinidine to the growth medium [34].
  • Loss of phosphorylation at Ser(421) and Ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of HDAC1 [33].
  • Overexpression of a constitutively active PKCalpha (PKCalpha CA) strongly activated LHR transcription in MCF-7 cells (devoid of PKCalpha), induced Sp1 phosphorylation at serine residue (s) and caused derecruitment of HDAC1/mSin3A complex from the promoter [35].

Physical interactions of HDAC1


Regulatory relationships of HDAC1


Other interactions of HDAC1

  • Coimmunoprecipitation experiments indicate that HDAC1 and HDAC2 are associated with Topo II in vivo under normal physiological conditions [45].
  • Finally, the histone deacetylase inhibitor trichostatin A (ref. 17) relieves transcriptional repression mediated by EED, but not by HPC2, a human homologue of polycomb [46].
  • MTA2 modulates the enzymatic activity of the histone deacetylase core complex [47].
  • These results define SAP30 as a component of a histone deacetylase complex conserved among eukaryotic organisms [48].
  • Here we report the identification of metastatic-associated protein 1 (MTA1), a component of histone deacetylase (HDAC) and nucleosome-remodelling complexes, as a gene product induced by heregulin-beta1 (HRG) [40].

Analytical, diagnostic and therapeutic context of HDAC1


  1. ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex. Wang, J., Hoshino, T., Redner, R.L., Kajigaya, S., Liu, J.M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. Counterregulation of chromatin deacetylation and histone deacetylase occupancy at the integrated promoter of human immunodeficiency virus type 1 (HIV-1) by the HIV-1 repressor YY1 and HIV-1 activator Tat. He, G., Margolis, D.M. Mol. Cell. Biol. (2002) [Pubmed]
  3. Endogenous inhibition of histone deacetylase 1 by tumor-suppressive maspin. Li, X., Yin, S., Meng, Y., Sakr, W., Sheng, S. Cancer Res. (2006) [Pubmed]
  4. Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1. Huang, B.H., Laban, M., Leung, C.H., Lee, L., Lee, C.K., Salto-Tellez, M., Raju, G.C., Hooi, S.C. Cell Death Differ. (2005) [Pubmed]
  5. A 13-amino acid amphipathic alpha-helix is required for the functional interaction between the transcriptional repressor Mad1 and mSin3A. Eilers, A.L., Billin, A.N., Liu, J., Ayer, D.E. J. Biol. Chem. (1999) [Pubmed]
  6. Mutation analysis of the HDAC 1, 2, 8 and CDKL5 genes in Rett syndrome patients without mutations in MECP2. Huppke, P., Ohlenbusch, A., Brendel, C., Laccone, F., Gärtner, J. Am. J. Med. Genet. A (2005) [Pubmed]
  7. Mitochondrial-dependent Ca2+ handling in Huntington's disease striatal cells: effect of histone deacetylase inhibitors. Oliveira, J.M., Chen, S., Almeida, S., Riley, R., Gon??alves, J., Oliveira, C.R., Hayden, M.R., Nicholls, D.G., Ellerby, L.M., Rego, A.C. J. Neurosci. (2006) [Pubmed]
  8. Remodeling chromatin and stress resistance in the central nervous system: histone deacetylase inhibitors as novel and broadly effective neuroprotective agents. Langley, B., Gensert, J.M., Beal, M.F., Ratan, R.R. Current drug targets. CNS and neurological disorders. (2005) [Pubmed]
  9. Cell cycle blockade and differentiation of ovarian cancer cells by the histone deacetylase inhibitor trichostatin A are associated with changes in p21, Rb, and Id proteins. Strait, K.A., Dabbas, B., Hammond, E.H., Warnick, C.T., Iistrup, S.J., Ford, C.D. Mol. Cancer Ther. (2002) [Pubmed]
  10. B56 regulatory subunit of protein phosphatase 2A mediates valproic acid-induced p300 degradation. Chen, J., St-Germain, J.R., Li, Q. Mol. Cell. Biol. (2005) [Pubmed]
  11. A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition. Ropero, S., Fraga, M.F., Ballestar, E., Hamelin, R., Yamamoto, H., Boix-Chornet, M., Caballero, R., Alaminos, M., Setien, F., Paz, M.F., Herranz, M., Palacios, J., Arango, D., Orntoft, T.F., Aaltonen, L.A., Schwartz, S., Esteller, M. Nat. Genet. (2006) [Pubmed]
  12. In vino veritas: a tale of two sirt1s? Koo, S.H., Montminy, M. Cell (2006) [Pubmed]
  13. APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Miaczynska, M., Christoforidis, S., Giner, A., Shevchenko, A., Uttenweiler-Joseph, S., Habermann, B., Wilm, M., Parton, R.G., Zerial, M. Cell (2004) [Pubmed]
  14. Acetylation inactivates the transcriptional repressor BCL6. Bereshchenko, O.R., Gu, W., Dalla-Favera, R. Nat. Genet. (2002) [Pubmed]
  15. Recruitment of O-GlcNAc transferase to promoters by corepressor mSin3A: coupling protein O-GlcNAcylation to transcriptional repression. Yang, X., Zhang, F., Kudlow, J.E. Cell (2002) [Pubmed]
  16. Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor alpha. Kawai, H., Li, H., Avraham, S., Jiang, S., Avraham, H.K. Int. J. Cancer (2003) [Pubmed]
  17. 5-Aza-2'-deoxycytidine (decitabine) can relieve p21WAF1 repression in human acute myeloid leukemia by a mechanism involving release of histone deacetylase 1 (HDAC1) without requiring p21WAF1 promoter demethylation. Scott, S.A., Dong, W.F., Ichinohasama, R., Hirsch, C., Sheridan, D., Sanche, S.E., Geyer, C.R., Decoteau, J.F. Leuk. Res. (2006) [Pubmed]
  18. Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO. Gelmetti, V., Zhang, J., Fanelli, M., Minucci, S., Pelicci, P.G., Lazar, M.A. Mol. Cell. Biol. (1998) [Pubmed]
  19. The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1. Rosato, R.R., Almenara, J.A., Grant, S. Cancer Res. (2003) [Pubmed]
  20. Epstein-Barr virus nuclear antigen 3C recruits histone deacetylase activity and associates with the corepressors mSin3A and NCoR in human B-cell lines. Knight, J.S., Lan, K., Subramanian, C., Robertson, E.S. J. Virol. (2003) [Pubmed]
  21. Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Magnaghi-Jaulin, L., Groisman, R., Naguibneva, I., Robin, P., Lorain, S., Le Villain, J.P., Troalen, F., Trouche, D., Harel-Bellan, A. Nature (1998) [Pubmed]
  22. Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. Yoo, Y.G., Kong, G., Lee, M.O. EMBO J. (2006) [Pubmed]
  23. Cell cycle regulation of chromatin at an origin of DNA replication. Zhou, J., Chau, C.M., Deng, Z., Shiekhattar, R., Spindler, M.P., Schepers, A., Lieberman, P.M. EMBO J. (2005) [Pubmed]
  24. Attenuation of a phosphorylation-dependent activator by an HDAC-PP1 complex. Canettieri, G., Morantte, I., Guzmán, E., Asahara, H., Herzig, S., Anderson, S.D., Yates, J.R., Montminy, M. Nat. Struct. Biol. (2003) [Pubmed]
  25. The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression. Ashburner, B.P., Westerheide, S.D., Baldwin, A.S. Mol. Cell. Biol. (2001) [Pubmed]
  26. A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: inhibition of the myogenic program. Mal, A., Sturniolo, M., Schiltz, R.L., Ghosh, M.K., Harter, M.L. EMBO J. (2001) [Pubmed]
  27. Histone deacetylase 1 can repress transcription by binding to Sp1. Doetzlhofer, A., Rotheneder, H., Lagger, G., Koranda, M., Kurtev, V., Brosch, G., Wintersberger, E., Seiser, C. Mol. Cell. Biol. (1999) [Pubmed]
  28. Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1. Duan, Z., Zarebski, A., Montoya-Durango, D., Grimes, H.L., Horwitz, M. Mol. Cell. Biol. (2005) [Pubmed]
  29. Transforming growth factor-beta1 recruits histone deacetylase 1 to a p130 repressor complex in transgenic mice in vivo. Bouzahzah, B., Fu, M., Iavarone, A., Factor, V.M., Thorgeirsson, S.S., Pestell, R.G. Cancer Res. (2000) [Pubmed]
  30. Role of histone deacetylation in cell-specific expression of endothelial nitric-oxide synthase. Gan, Y., Shen, Y.H., Wang, J., Wang, X., Utama, B., Wang, J., Wang, X.L. J. Biol. Chem. (2005) [Pubmed]
  31. Histone deacetylase activity represses gamma interferon-inducible HLA-DR gene expression following the establishment of a DNase I-hypersensitive chromatin conformation. Osborne, A., Zhang, H., Yang, W.M., Seto, E., Blanck, G. Mol. Cell. Biol. (2001) [Pubmed]
  32. Receptor-interacting protein 140 directly recruits histone deacetylases for gene silencing. Wei, L.N., Hu, X., Chandra, D., Seto, E., Farooqui, M. J. Biol. Chem. (2000) [Pubmed]
  33. Histone deacetylase 1 phosphorylation promotes enzymatic activity and complex formation. Pflum, M.K., Tong, J.K., Lane, W.S., Schreiber, S.L. J. Biol. Chem. (2001) [Pubmed]
  34. Rapid induction of histone hyperacetylation and cellular differentiation in human breast tumor cell lines following degradation of histone deacetylase-1. Zhou, Q., Melkoumian, Z.K., Lucktong, A., Moniwa, M., Davie, J.R., Strobl, J.S. J. Biol. Chem. (2000) [Pubmed]
  35. Protein kinase Calpha-induced derepression of the human luteinizing hormone receptor gene transcription through ERK-mediated release of HDAC1/Sin3A repressor complex from Sp1 sites. Liao, M., Zhang, Y., Dufau, M.L. Mol. Endocrinol. (2008) [Pubmed]
  36. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Ng, H.H., Zhang, Y., Hendrich, B., Johnson, C.A., Turner, B.M., Erdjument-Bromage, H., Tempst, P., Reinberg, D., Bird, A. Nat. Genet. (1999) [Pubmed]
  37. The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase. Ferreira, R., Magnaghi-Jaulin, L., Robin, P., Harel-Bellan, A., Trouche, D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  38. BRCA1 interacts with components of the histone deacetylase complex. Yarden, R.I., Brody, L.C. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  39. The tumor suppressor p53 and histone deacetylase 1 are antagonistic regulators of the cyclin-dependent kinase inhibitor p21/WAF1/CIP1 gene. Lagger, G., Doetzlhofer, A., Schuettengruber, B., Haidweger, E., Simboeck, E., Tischler, J., Chiocca, S., Suske, G., Rotheneder, H., Wintersberger, E., Seiser, C. Mol. Cell. Biol. (2003) [Pubmed]
  40. Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Mazumdar, A., Wang, R.A., Mishra, S.K., Adam, L., Bagheri-Yarmand, R., Mandal, M., Vadlamudi, R.K., Kumar, R. Nat. Cell Biol. (2001) [Pubmed]
  41. RBP1 recruits the mSIN3-histone deacetylase complex to the pocket of retinoblastoma tumor suppressor family proteins found in limited discrete regions of the nucleus at growth arrest. Lai, A., Kennedy, B.K., Barbie, D.A., Bertos, N.R., Yang, X.J., Theberge, M.C., Tsai, S.C., Seto, E., Zhang, Y., Kuzmichev, A., Lane, W.S., Reinberg, D., Harlow, E., Branton, P.E. Mol. Cell. Biol. (2001) [Pubmed]
  42. Histone deacetylase 1/mSin3A disrupts gamma interferon-induced CIITA function and major histocompatibility complex class II enhanceosome formation. Zika, E., Greer, S.F., Zhu, X.S., Ting, J.P. Mol. Cell. Biol. (2003) [Pubmed]
  43. Sp1 and Sp3 recruit histone deacetylase to repress transcription of human telomerase reverse transcriptase (hTERT) promoter in normal human somatic cells. Won, J., Yim, J., Kim, T.K. J. Biol. Chem. (2002) [Pubmed]
  44. Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor. Gaughan, L., Logan, I.R., Cook, S., Neal, D.E., Robson, C.N. J. Biol. Chem. (2002) [Pubmed]
  45. Histone deacetylase interacts directly with DNA topoisomerase II. Tsai, S.C., Valkov, N., Yang, W.M., Gump, J., Sullivan, D., Seto, E. Nat. Genet. (2000) [Pubmed]
  46. Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. van der Vlag, J., Otte, A.P. Nat. Genet. (1999) [Pubmed]
  47. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Zhang, Y., Ng, H.H., Erdjument-Bromage, H., Tempst, P., Bird, A., Reinberg, D. Genes Dev. (1999) [Pubmed]
  48. SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex. Zhang, Y., Sun, Z.W., Iratni, R., Erdjument-Bromage, H., Tempst, P., Hampsey, M., Reinberg, D. Mol. Cell (1998) [Pubmed]
  49. A role for histone deacetylase activity in HDAC1-mediated transcriptional repression. Hassig, C.A., Tong, J.K., Fleischer, T.C., Owa, T., Grable, P.G., Ayer, D.E., Schreiber, S.L. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  50. Histone deacetylase activity is retained in primary neurons expressing mutant huntingtin protein. Hoshino, M., Tagawa, K., Okuda, T., Murata, M., Oyanagi, K., Arai, N., Mizutani, T., Kanazawa, I., Wanker, E.E., Okazawa, H. J. Neurochem. (2003) [Pubmed]
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