HDAC3
Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene. [provided by RefSeq, Jul 2008]
Function
Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates (PubMed:23911289, PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28497810, PubMed:28167758).
Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:23911289).
Histone deacetylases act via the formation of large multiprotein complexes (PubMed:23911289).
Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression (PubMed:23911289).
Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (By similarity).
Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI3K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803).
Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (By similarity).
During the activation phase, promotes the accumulation of ubiquitinated ARNTL/BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and ARNTL/BMAL1 (By similarity).
The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity).
Also functions as deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14 and RARA (PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28167758).
Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (PubMed:28167758).
In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758).
In addition to protein deacetylase activity, also acts as protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:34608293).
Catalyzes decrotonylation of MAPRE1/EB1 (PubMed:34608293).
Biological Process
Cellular response to fluid shear stress Source: UniProtKB
Chromatin organization Source: UniProtKB
Circadian regulation of gene expression Source: UniProtKB
Histone H3 deacetylation Source: GO_Central
Histone H4 deacetylation Source: GO_Central
Negative regulation of apoptotic process Source: ProtInc
Negative regulation of JNK cascade Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of cold-induced thermogenesis Source: YuBioLab
Positive regulation of protein import into nucleus Source: UniProtKB
Positive regulation of protein phosphorylation Source: UniProtKB
Positive regulation of protein ubiquitination Source: UniProtKB
Positive regulation of TOR signaling Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Protein deacetylation Source: UniProtKB
Regulation of circadian rhythm Source: UniProtKB
Regulation of protein stability Source: UniProtKB
Spindle assembly Source: UniProtKB
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Datasheet