HDAC3

Description

The HDAC3 (histone deacetylase 3) is a protein-coding gene located on chromosome 5.

Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice. Histones are proteins that package DNA into nucleosomes, and their acetylation and deacetylation play a key role in regulating gene expression. HDAC3 is a Class I histone deacetylase that is found in the cell nucleus and is particularly involved in modulating the activities of nuclear receptors. HDAC3 is known to interact with various proteins, forming complexes that regulate gene expression. Studies in mice with a deletion of HDAC3 in intestinal epithelial cells show that it is important for intestinal health, affecting the function of these cells and the composition of gut bacteria.

HDAC3 is a histone deacetylase that removes acetyl groups from lysine residues on histone proteins (H2A, H2B, H3, and H4) and other non-histone proteins. This deacetylation process is crucial for epigenetic regulation, affecting gene expression, cell cycle progression, and developmental processes. HDAC3 functions within large multiprotein complexes. It plays a role in repressing gene expression by deacetylating H3K27 on enhancer elements, counteracting the activity of EP300 acetyltransferase. HDAC3 acts as a chaperone, transporting phosphorylated NR2C1 to PML bodies for sumoylation. It collaborates with XBP1 isoform 1 to activate NFE2L2-mediated HMOX1 expression, promoting endothelial cell survival under oxidative stress. HDAC3 regulates the circadian clock by promoting BMAL1 accumulation and blocking CRY1/2 ubiquitination, influencing the expression of BMAL1 and lipid metabolism genes. It also deacetylates non-histone targets like KAT5, MEF2D, MAPK14, RARA, and STAT3. HDAC3 acts as a corepressor of RARA, inhibiting its DNA binding. Additionally, HDAC3 deacetylates and represses microRNA-10a, impacting the inflammatory response. HDAC3 exhibits protein-lysine deacylase activity, removing crotonyl and 2-hydroxyisobutyryl groups from lysine residues, influencing decrotonylation and de-2-hydroxyisobutyrylation processes. It specifically decrotonylates MAPRE1/EB1.

HDAC3 is also known as HD3, KDAC3, RPD3, RPD3-2.

Associated Diseases

WES Whole Exome Sequencing