background:
Reversible acetylation of highly conserved lysine residues within the N-terminal tail domains of core histones, plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone acetylation is a dynamic process determined by the net activities of histone acetyltransferases (HATs) and the competing enzymes histone deacetylases (HDACs). Histone deacetylases activities are often, but not always, associated with transcriptional repression and nucleosomal condensations. Recruitment of the multiprotein complexes to promoter sites occurs by many sequence specific DNA-binding proteins such as unliganded nuclear hormone receptors, DP1-E2F, YY1 and Rb family of transcription factors, transcriptional repressors and tumor suppressors (e.g. BRCA1). Aberrant recruitment of HDACs by certain oncoproteins may occur in certain neoplastic diseases. Belongs to the histone deacetylase family. Type 1.
Function:
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development.
Subunit:
Component of a RCOR/GFI/KDM1A/HDAC complex. Interacts directly with GFI1 and GFI1B. Interacts with SNW1, HDAC7, PRDM6, SAP30, SETDB1 and SUV39H1. Interacts with the H2AFY (via the non-histone region). Part of the core histone deacetylase (HDAC) complex composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core complex associates with MTA2, MBD3, MTA1L1, CHD3 and CHD4 to form the nucleosome remodeling and histone deacetylation (NuRD) complex, or with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex. Component of a SHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A. The SHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Part of a complex containing the core histones H2A, H2B, H3 and H4, DEK and unphosphorylated DAXX. Part of a complex containing ATR and CHD4. Forms a heterologous complex at least with YY1. Interacts with ATR, CSFA2T3, DNMT1, MINT, HDAC10, HCFC1, NRIP1, KDM4A and PELP1. Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3, ARID4B, HDAC1 and HDAC2. Interacts with CHFR and SAP30L. Interacts (CK2 phosphorylated form) with SP3. Interacts with TSHZ3 (via its N-terminus). Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2.
Subcellular Location:
Nucleus.
Tissue Specificity:
Widely expressed; lower levels in brain and lung.
Post-translational modifications:
S-nitrosylated by GAPDH. In neurons, S-Nitrosylation at Cys-262 and Cys-274 does not affect the enzyme activity but abolishes chromatin-binding, leading to increases acetylation of histones and activate genes that are associated with neuronal development. In embryonic cortical neurons, S-Nitrosylation regulates dendritic growth and branching.
Similarity:
Belongs to the histone deacetylase family. HD type 1 subfamily.
Database links:
Entrez Gene: 3065 Human
Entrez Gene: 433759 Mouse
Entrez Gene: 297893 Rat
Entrez Gene: 404126 Cow
Omim: 601241 Human
SwissProt: Q32PJ8 Cow
SwissProt: Q13547 Human
SwissProt: O09106 Mouse
SwissProt: Q4QQW4 Rat
Unigene: 88556 Human
Unigene: 202504 Mouse
Unigene: 391033 Mouse
Unigene: 1863 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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