HDAC3

HDAC3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4A69
Identifiers
Aliases	HDAC3 , HD3, RPD3, RPD3-2, histone deacetylase 3
External IDs	OMIM: 605166; MGI: 1343091; HomoloGene: 48250; GeneCards: HDAC3; OMA:HDAC3 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) [1] Band n/a Start 141,620,876 bp [1] End 141,636,870 bp [1]
Gene location (Mouse) Chr. Chromosome 18 (mouse) [2] Band 18 19.81 cM|18 B3 Start 38,068,897 bp [2] End 38,088,069 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum right adrenal cortex left adrenal gland left adrenal cortex skin of leg granulocyte skin of abdomen anterior pituitary right ovary right lobe of thyroid gland Top expressed in spermatocyte ventricular zone genital tubercle tail of embryo superior frontal gyrus muscle of thigh lip yolk sac primary visual cortex neural tube More reference expression data BioGPS More reference expression data
Gene ontology Molecular function NAD-dependent histone deacetylase activity (H3-K14 specific) transcription corepressor activity histone deacetylase activity protein deacetylase activity transcription factor binding histone deacetylase binding chromatin binding NF-kappaB binding protein binding enzyme binding hydrolase activity cyclin binding Cellular component cytoplasm histone deacetylase complex cytosol Golgi apparatus plasma membrane transcription repressor complex nucleoplasm spindle microtubule nucleus mitotic spindle Biological process histone H3 deacetylation positive regulation of protein phosphorylation regulation of transcription, DNA-templated regulation of protein stability negative regulation of apoptotic process negative regulation of transcription by RNA polymerase II cellular response to fluid shear stress transcription, DNA-templated spindle assembly protein deacetylation negative regulation of JNK cascade circadian rhythm negative regulation of myotube differentiation negative regulation of transcription, DNA-templated histone deacetylation positive regulation of TOR signaling positive regulation of transcription by RNA polymerase II negative regulation of nucleic acid-templated transcription regulation of lipid metabolic process chromatin organization positive regulation of protein import into nucleus histone H4 deacetylation positive regulation of cold-induced thermogenesis positive regulation of protein ubiquitination circadian regulation of gene expression regulation of circadian rhythm rhythmic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8841 15183 Ensembl ENSG00000171720 ENSMUSG00000024454 UniProt O15379 O88895 RefSeq (mRNA) NM_003883 NM_010411 RefSeq (protein) NP_003874 NP_001341968 NP_001341969 NP_001341970 NP_034541 Location (UCSC) Chr 5: 141.62 – 141.64 Mb Chr 18: 38.07 – 38.09 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice. ^{[5] [6] [7] [8]}

Function

Histones are alkaline positively charged proteins that package and organize DNA into structural units known as nucleosomes, the primary protein component of chromatin. ^[9] Posttranslational, enzyme-mediated lysine acetylation and deacetylation of histone tails modify local chromatin structure by altering the electrostatic interaction between the negatively charged DNA backbone and the histones. ^{[10] [11]} HDAC3 is a Class I member of the histone deacetylase superfamily, which is divided into four classes based on function and sequence homology. ^[12] HDAC3 is recruited to enhancers, where it modulates the epigenome and regulates nearby gene expression. It is found exclusively in the cell nucleus, and is the only endogenous histone deacetylase biochemically purified as part of the nuclear receptor corepressor complex containing NCOR and SMRT (NCOR2). Unlike other HDACs, HDAC3 therefore plays a distinct role in regulating the transcriptional activity of nuclear receptors. ^[12]

Role in intestinal homeostasis

Histone deacetylases can be regulated by endogenous factors, dietary components, synthetic inhibitors, and bacteria-derived signals. Studies in mice with a specific deletion of HDAC3 in intestinal epithelial cells (IECs) have shown deregulated gene expression in IECs. In these deletion-mutant mice, the loss of Paneth cells, impaired IEC function, and changes in the intestinal composition of commensal bacteria were observed. These adverse effects did not occur in germ-free mice, indicating that they depend on intestinal microbial colonization. However, they are not caused by the presence of an altered microbiota, since normal germ-free mice colonized with the mutant-associated microbiota did not develop the same defects.

Although the precise mechanisms and signals remain unclear, HDAC3 is known to interact with commensal bacteria–derived signals from the gut microbiota. These interactions calibrate epithelial cell responses that are essential for establishing a balanced relationship between the host and its commensal microbes and for maintaining intestinal homeostasis. ^{[13] [14] [15] [16]}

Interactions

HDAC3 has been shown to interact with:

• CBFA2T3, ^{[17] [18]}
• CCND1, ^{[19] [20]}
• GATA1, ^[21]
• GATA2, ^[22]
• GPS2, ^[23]
• GTF2I, ^{[24] [25]}
• HDAC4, ^{[26] [27] [28] [29]}
• HDAC5, ^{[23] [27] [28] [29]}
• HDAC7A, ^[26]
• HDAC9, ^{[30] [31]}
• MAP3K7IP2, ^[32]
• MAPK11, ^[33]
• NCOR1, ^{[23] [26] [28] [34] [35] [36] [37]}
• NCOR2, ^{[28] [34] [35] [36] [37] [38] [39]}
• PPARD, ^{[40] [41]}
• PPARG, ^{[40] [42]}
• PML ^[43]
• RBBP4, ^[44]
• RELA, ^[45]
• RP, ^{[42] [46]}
• RUNX2, ^[47]
• SUV39H1, ^[48]
• TCP1, ^[39]
• TBL1X, ^{[23] [38]}
• TR2, ^{[40] [49] [50]}
• UBC, ^[51]
• YY1, ^{[52] [53]} and
• ZBTB33. ^[34]

See also

• Histone deacetylase

References

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2. GRCm38: Ensembl release 89: ENSMUSG00000024454 – Ensembl, May 2017
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Further reading

• Verdin E, Dequiedt F, Kasler HG (May 2003). "Class II histone deacetylases: versatile regulators". Trends in Genetics. 19 (5): 286–293. doi:10.1016/S0168-9525(03)00073-8. hdl: 2268/80861 . PMID   12711221.

External links

• HDAC3+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.