Chromatin Regulator | Alias |
| HDAC1 | HD1; RPD3; GON-10; RPD3L1; DKFZp686H12203 |
External Links: | Wiki GeneCards NCBI UniProt |
Related histone modifications: | H2AK5ac;H3K4ac;H3K14ac;H3K27ac;H3K56ac;H4K5ac;H4K8ac;H4K12ac;H4K16ac |
Introduction | |
| Full Name: Histone deacetylase 1
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HDAC1 is a zinc-dependent class I histone deacetylase. It possesses a highly conserved deacetylase domain and is often found to coexist with HDAC2 in the CoREST, NuRD, and Sin3 complexes and performs redundant functions with HDAC2 during later development. HDAC1 plays roles in transcriptional modulation, immune responses, tumor progression, development, DNA damage, and organogenesis (1-16).
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Function and Interaction | |
| HDAC1 interacts with the signal transducer and activator of transcription (STAT) 1 and 2 subunits of ISGF3 and participates in the positive control of IFN-α /β-responsive genes (1). HDAC1 has been shown to be involved in NF-κB-signaling pathways, as it is capable of deacetylating p65 and reducing the transcription and the nuclear export of NF-κB (2-3). The HDAC1/HDAC2 dimer interacts with EZH2, assisting EZH2 in its interaction with Snail, thus forming the EZH2/HDAC1/ HDAC 2/Snail complex, which may be related to the progression of nasopharyngeal carcinoma (NPC) (4). HDAC1 is essential during epidermal development and suppresses the activity of p53 and p63 in epidermal progenitor cells (5). Inhibition of both HDAC1 and HDAC2 can result in increased numbers of synapses and excitatory synapse maturation (6). P25/Cdk5 can disorganize the function of HDAC1 in neurons, leading to DNA damage and cell death (7). HDAC1 deletion can cause embryonic lethality and is also related to organogenesis, specifically being involved in myocardial growth, morphogenesis, and contractility (8).
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Disease Association | |
| HDAC1 is associated with a poor prognosis and is highly expressed in many cancers, such as renal cell cancer, prostate cancer, pancreatic carcinoma, gastric cancer, and breast carcinomas (3,9-14).
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ChIP-Seq data
ChIP-Seq data of related histone modifications
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References | |
1. Nusinzon, I. and Horvath, C.M. (2003) Interferon-stimulated transcription and innate antiviral immunity require deacetylase activity and histone deacetylase 1. P Natl Acad Sci USA, 100, 14742-14747.
2. Calao, M., Burny, A., Quivy, V., Dekoninck, A. and Van Lint, C. (2008) A pervasive role of histone acetyltransferases and deacetylases in an NF-kappa B-signaling code. Trends Biochem Sci, 33, 339-349.
3. Spiegel, S., Milstien, S. and Grant, S. (2012) Endogenous modulators and pharmacological inhibitors of histone deacetylases in cancer therapy. Oncogene, 31, 537-551.
4. Tong, Z.T., Cai, M.Y., Wang, X.G., Kong, L.L., Mai, S.J., Liu, Y.H., Zhang, H.B., Liao, Y.J., Zheng, F., Zhu, W. et al. (2012) EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin. Oncogene, 31, 583-594.
5. LeBoeuf, M., Terrell, A., Trivedi, S., Sinha, S., Epstein, J.A., Olson, E.N., Morrisey, E.E. and Millar, S.E. (2010) Hdac1 and Hdac2 Act Redundantly to Control p63 and p53 Functions in Epidermal Progenitor Cells. Dev Cell, 19, 807-818.
6. Akhtar, M.W., Raingo, J., Nelson, E.D., Montgomery, R.L., Olson, E.N., Kavalali, E.T. and Monteggia, L.M. (2009) Histone Deacetylases 1 and 2 Form a Developmental Switch That Controls Excitatory Synapse Maturation and Function. J Neurosci, 29, 8288-8297.
7. Kim, D., Frank, C.L., Dobbin, M.M., Tsunemoto, R.K., Tu, W., Peng, P.L., Guan, J.S., Lee, B.H., Moy, L.Y., Giusti, P. et al. (2008) Deregulation of HDAC1 by p25/Cdk5 in Neurotoxicity. Neuron, 60, 803-817.
8. Montgomery, R.L., Davis, C.A., Potthoff, M.J., Haberland, M., Fielitz, J., Qi, X.X., Hill, J.A., Richardson, J.A. and Olson, E.N. (2007) Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Gene Dev, 21, 1790-1802.
9. Fritzsche, F.R., Weichert, W., Roske, A., Gekeler, V., Beckers, T., Stephan, C., Jung, K., Scholman, K., Denkert, C., Dietel, M. et al. (2008) Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer. Bmc Cancer, 8.
10. Weichert, W., Roske, A., Gekeler, V., Beckers, T., Stephan, C., Jung, K., Fritzsche, F.R., Niesporek, S., Denkert, C., Dietel, M. et al. (2008) Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy. Brit J Cancer, 98, 604-610.
11. Miyake, K., Yoshizumi, T., Imura, S., Sugimoto, K., Batmunkh, E., Kanemura, H., Morine, Y. and Shimada, M. (2008) Expression of hypoxia-inducible factor-1alpha, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma: correlation with poor prognosis with possible regulation. Pancreas, 36, e1-9.
12. Choi, J.H., Kwon, H.J., Yoon, B.I., Kim, J.H., Han, S.U., Joo, H.J. and Kim, D.Y. (2001) Expression profile of histone deacetylase 1 in gastric cancer tissues. Jpn J Cancer Res, 92, 1300-1304.
13. Zhang, Z., Yamashita, H., Toyama, T., Sugiura, H., Ando, Y., Mita, K., Hamaguchi, M., Hara, Y., Kobayashi, S. and Iwase, H. (2005) Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast*. Breast Cancer Res Treat, 94, 11-16.
14. Rikimaru, T., Taketomi, A., Yamashita, Y., Shirabe, K., Hamatsu, T., Shimada, M. and Maehara, Y. (2007) Clinical significance of histone deacetylase 1 expression in patients with hepatocellular carcinoma. Oncology, 72, 69-74.
15. Yang, X.J. and Seto, E. (2008) The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol, 9, 206-218.
16. Hassig, C.A., Tong, J.K., Fleischer, T.C., Owa, T., Grable, P.G., Ayer, D.E. and Schreiber, S.L. (1998) A role for histone deacetylase activity in HDAC1-mediated transcriptional repression. Proc Natl Acad Sci U S A, 95, 3519-3524.
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