HDAC3

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

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
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Function

Histones are highly alkaline proteins that package and order DNA into structural units called nucleosomes, which comprise the major protein component of chromatin. The posttranslational and enzymatically mediated lysine acetylation and deacetylation of histone tails change the local chromatin structure by altering the electrostatic attraction between the negatively charged DNA backbone and histones. HDAC3 is a Class I member of the histone deacetylase superfamily (comprising four classes based on function and DNA sequence homology) that is recruited to enhancers to modulate both the epigenome and nearby gene expression. HDAC3 is found exclusively in the cell nucleus, where it is the sole endogenous histone deacetylase biochemically purified in the nuclear-receptor corepressor complex containing NCOR and SMRT (NCOR2). Thus, HDAC3, unlike other HDACs, has a unique role in modulating the transcriptional activities of nuclear receptors.

Alternative functions

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) show a deregulated IEC's gene expression. In these deletion-mutant mice, loss of Paneth cells, impaired IEC function and alterations in intestinal composition of commensal bacteria were observed. These negative effects were not observed in germ-free mice, indicating that the effects of the deletion are only seen in the presence of intestinal microbial colonization. But the negative effects of HDAC3 deletion are not due to the presence of an altered microbiota because normal germ-free mice colonized with the altered microbiota did not show the negative effects seen in deletion mutants.

Although the precise mechanism and the specific signals are not known it is clear that HDAC3 interacts with derived signals of commensal bacteria of the gut microbiota. These interactions are responsible of calibrating epithelial cells responses necessary to establish a normal relationship between the host and the commensal as well as to maintain intestinal homeostasis.^{[9][10][11][12]}

Interactions

HDAC3 has been shown to interact with:

• CBFA2T3,^[13][14]
• CCND1,^[15][16]
• GATA1,^[17]
• GATA2,^[18]
• GPS2,^[19]
• GTF2I,^[20][21]
• HDAC4,^{[22][23][24][25]}
• HDAC5,^{[19][23][24][25]}
• HDAC7A,^[22]
• HDAC9,^[26][27]
• MAP3K7IP2,^[28]
• MAPK11,^[29]
• NCOR1,^{[19][22][24][30][31][32][33]}
• NCOR2,^{[24][30][31][32][33][34][35]}
• PPARD,^[36][37]
• PPARG,^[36][38]
• PML^[39]
• RBBP4,^[40]
• RELA,^[41]
• RP,^[38][42]
• RUNX2,^[43]
• SUV39H1,^[44]
• TCP1,^[35]
• TBL1X,^[19][34]
• TR2,^[36][45][46]
• UBC,^[47]
• YY1,^[48][49] and
• ZBTB33.^[30]

See also

• Histone deacetylase