Protein-coding gene in humans
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
References
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^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024454 – Ensembl , May 2017
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Further reading
External links
This article incorporates text from the United States National Library of Medicine , which is in the public domain .
Activity Regulation Classification Kinetics Types