HDAC3 explained

Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice.[1] [2] [3] [4]

Function

Histones are alkaline positively charged proteins that package and organize DNA into structural units known as nucleosomes, the primary protein component of chromatin.[5] 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.[6] [7] HDAC3 is a Class I member of the histone deacetylase superfamily, which is divided into four classes based on function and sequence homology.[8] 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.

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.[9] [10] [11] [12]

Interactions

HDAC3 has been shown to interact with:

See also

Further reading

Notes and References

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