Histone deacetylase 9 is an enzyme that in humans is encoded by the HDAC9 gene. [5] [6] [7]
Histone deacetylase 9 is an enzyme that in humans is encoded by the HDAC9 gene. [5] [6] [7]
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. [7]
Histone deacetylase 9 (HDAC9), a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions.
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.
HDAC9 and BCL2L11 are upregulated while miR-92a was downregulated in clinical samples and rat models of intracranial aneurysm (IA). HDAC9 inhibition or miR-92a elevation improved pathological changes and repressed apoptosis and expression of MMP-2, MMP-9, VEGF and inflammatory factors in vascular tissues from IA rats. Oppositely, HDAC9 overexpression or miR-92a reduction had contrary effects. miR-92a downregulation reversed the effect of silenced HDAC9 on IA rats. HDAC9 inhibition upregulates miR-92a to repress the progression of IA via silencing BCL2L11. [8]
Data partially confirmed earlier results and showed that variants in CDKN2B-AS1, RP1, and HDAC9 could be genetic susceptibility factors for IA in a Chinese population. [9]
Histone deacetylase 9 (HDAC9) has been reported to be elevated in ischemic brain injury, but its mechanism in stroke is still enigmatic. CTCF inhibited miR-383-5p expression via its enrichment in the promoter region of miR-383-5p, whereas the miR-383-5p targeted and inhibited HDAC9 expression. [10] In the oxygen glucose deprivation cell model and the middle cerebral artery occlusion rat model, elevation of HDAC9 is regulated by the CTCF/miR-383-5p/HDAC9 pathway mediated apoptosis induced by endoplasmic reticulum stress, while reduction of HDAC9 alleviated apoptosis and the symptoms of cerebral infarction in MCAO rats. Thus, the CTCF/miR-383-5p/HDAC9 pathway may present a target for drug development against ischemic brain injury 6). [11]
HDAC9 is highly expressed in MCAO mice and oxygen glucose deprivation (OGD) stimulated cells. Silencing of HDAC9 inhibited neuronal apoptosis and inflammatory factor release in vitro. HDAC9 downregulated miR-20a by enriching in its promoter region, while silencing of HDCA9 promoted miR-20a expression. miR-20a targeted Neurod1 and down-regulated its expression. Silencing of HDAC9 diminished OGD-induced neuronal apoptosis and inflammatory factor release in vitro as well as ischemic brain injury in vivo by regulating the miR-20a/NeuroD1 signaling. HDAC9 silencing may retard ischemic brain injury through miR-20a/Neurod1 signaling. [11]
HDAC9 is over-expressed in prognostically poor glioblastoma patients. Knockdown HDAC9 decreased proliferation in vitro and tumor formation in vivo. HDAC9 accelerated cell cycle in part by potentiating the EGFR signaling pathway. Also, HDAC9 interacted with TAZ, a key downstream effector of Hippo pathway. Knockdown of HDAC9 decreased the expression of TAZ. We found that overexpressed TAZ in HDAC9-knockdown cells abrogated the effects induced by HDAC9 silencing both in vitro and in vivo. HDAC9 promotes tumor formation of glioblastoma via TAZ-mediated EGFR pathway activation. [12]
HDAC9 was suggested to contribute to developmental delay in Saethre-Chotzen syndrome (SCS) patients with 7p21 mirodeletions. [13]
Motor innervation controls chromatin acetylation in skeletal muscle and that histone deacetylase 9 (HDAC9) is a signal-responsive transcriptional repressor which is downregulated upon denervation, with consequent upregulation of chromatin acetylation and AChR expression. Forced expression of Hdac9 in denervated muscle prevents upregulation of activity-dependent genes and chromatin acetylation by linking myocyte enhancer factor 2 (MEF2) and class I HDACs. By contrast, Hdac9-null mice are supersensitive to denervation-induced changes in gene expression and show chromatin hyperacetylation and delayed perinatal downregulation of myogenin, an activator of AChR genes. These findings show a molecular mechanism to account for the control of chromatin acetylation by presynaptic neurons and the activity-dependent regulation of skeletal muscle genes by motor innervation. [14]
HDAC9 has been shown to interact with:
Histone deacetylases (EC 3.5.1.98, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on both histone and non-histone proteins. HDACs allow histones to wrap the DNA more tightly. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. HDAC's action is opposite to that of histone acetyltransferase. HDAC proteins are now also called lysine deacetylases (KDAC), to describe their function rather than their target, which also includes non-histone proteins. In general, they suppress gene expression.
Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 also known as EP300 or p300 is an enzyme that, in humans, is encoded by the EP300 gene. It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth.
Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.
In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that repress are known as corepressors. The mechanism of action of transcription coregulators is to modify chromatin structure and thereby make the associated DNA more or less accessible to transcription. In humans several dozen to several hundred coregulators are known, depending on the level of confidence with which the characterisation of a protein as a coregulator can be made. One class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second ATP dependent class modifies the conformation of chromatin.
Histone acetylation and deacetylation are the processes by which the lysine residues within the N-terminal tail protruding from the histone core of the nucleosome are acetylated and deacetylated as part of gene regulation.
Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene.
Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the HDAC2 gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones. As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy.
Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice.
Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.
Histone-binding protein RBBP4 is a protein that in humans is encoded by the RBBP4 gene.
Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the HDAC4 gene.
Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the MEF2C gene. MEF2C is a transcription factor in the Mef2 family.
C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the CTBP1 gene. CtBP1 is one of two CtBP proteins, the other protein being CtBP2.
Myocyte-specific enhancer factor 2A is a protein that in humans is encoded by the MEF2A gene. MEF2A is a transcription factor in the Mef2 family. In humans it is located on chromosome 15q26. Certain mutations in MEF2A cause an autosomal dominant form of coronary artery disease and myocardial infarction.
Histone deacetylase 5 is an enzyme that in humans is encoded by the HDAC5 gene.
Myocyte-specific enhancer factor 2D is a protein that in humans is encoded by the MEF2D gene.
Histone deacetylase 7 is an enzyme that in humans is encoded by the HDAC7 gene.
Metastasis-associated protein MTA2 is a protein that in humans is encoded by the MTA2 gene.
Calcineurin-binding protein cabin-1 is a protein that in humans is encoded by the CABIN1 gene.
Memory is commonly referred to as the ability to encode, store, retain and subsequently recall information and past experiences in the human brain. This process involves many proteins, one of which is the Histone-binding protein RbAp48, encoded by the RBBP4 gene in humans.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
