HDAC9

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 has sequence homology to members of the histone deacetylase family. This gene is orthologous to the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

Full Name

Histone Deacetylase 9

Function

Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Represses MEF2-dependent transcription.

Isoform 3 lacks active site residues and therefore is catalytically inactive. Represses MEF2-dependent transcription by recruiting HDAC1 and/or HDAC3. Seems to inhibit skeletal myogenesis and to be involved in heart development. Protects neurons from apoptosis, both by inhibiting JUN phosphorylation by MAPK10 and by repressing JUN transcription via HDAC1 recruitment to JUN promoter.

Biological Process

B cell activation Source: UniProtKB
B cell differentiation Source: UniProtKB
Cellular response to insulin stimulus Source: BHF-UCL
Cholesterol homeostasis Source: ARUK-UCL
Chromatin organization Source: UniProtKB-KW
Heart development Source: BHF-UCL
Histone deacetylation Source: BHF-UCL
Histone H3 deacetylation Source: BHF-UCL
Histone H4 deacetylation Source: BHF-UCL
Histone H4-K16 deacetylation Source: ARUK-UCL
Inflammatory response Source: UniProtKB
Negative regulation of cytokine production Source: ARUK-UCL
Negative regulation of lipoprotein lipase activity Source: ARUK-UCL
Negative regulation of transcription, DNA-templated Source: BHF-UCL
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Peptidyl-lysine deacetylation Source: BHF-UCL
Positive regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
Regulation of skeletal muscle fiber development Source: UniProtKB
Regulation of striated muscle cell differentiation Source: UniProtKB

Cellular Location

Nucleus

Involvement in disease

A chromosomal aberration involving HDAC9 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with TGFB2 resulting in lack of HDAC9 protein.

PTM

Phosphorylated on Ser-220 and Ser-450; which promotes 14-3-3-binding, impairs interaction with MEF2, and antagonizes antimyogenic activity. Phosphorylated on Ser-240; which impairs nuclear accumulation (By similarity). Isoform 7 is phosphorylated on Tyr-1010. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import.
Sumoylated.