HDAC3

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HDAC3
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HDAC3, HD3, RPD3, RPD3-2, histone deacetylase 3
External IDs MGI: 1343091 HomoloGene: 48250 GeneCards: HDAC3
Gene location (Human)
Chromosome 5 (human)
Chr. Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for HDAC3
Genomic location for HDAC3
Band n/a Start 141,620,876 bp[1]
End 141,636,870 bp[1]
RNA expression pattern
PBB GE HDAC3 216326 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003883

NM_010411

RefSeq (protein)

NP_003874
NP_001341968
NP_001341969
NP_001341970

n/a

Location (UCSC) Chr 5: 141.62 – 141.64 Mb Chr 5: 37.94 – 37.95 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Histone deacetylase 3 is an enzyme that in humans is encoded by the HDAC3 gene.[5][6]

Function[edit]

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.[7]

This enzyme is involved in the coordination of commensal-bacteria-dependent intestinal homeostasis when expressed in intestinal epithelial cells.

Function of HDAC3 gene can be effectively examined by siRNA knockdown based on an independent validation.[8]

Alternative functions[edit]

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) show a deregulated IEC's gene expression. In these deletion-mutant mice, loss of Paneth cells, impaired IEC function and alterations in intestinal composition of commensal bacteria were observed. These negative effects were not observed in germ-free mice, indicating that the effects of the deletion are only seen in the presence of intestinal microbial colonization. But the negative effects of HDAC3 deletion are not due to the presence of an altered microbiota because normal germ-free mice colonized with the altered microbiota did not show the negative effects seen in deletion mutants.

Although the precise mechanism and the specific signals are not known it is clear that HDAC3 interacts with derived signals of commensal bacteria of the gut microbiota. These interactions are responsible of calibrating epithelial cells responses necessary to establish a normal relationship between the host and the commensal as well as to maintain intestinal homeostasis.[9][10][11][12]

Model organisms[edit]

Model organisms have been used in the study of HDAC3 function. A conditional knockout mouse line, called Hdac3tm1a(EUCOMM)Wtsi[17][18] was generated as part of the International Knockout Mouse Consortium program, a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[19][20][21]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[15][22]

Twenty six tests were carried out on mutant mice and two significant abnormalities were observed.[15] No homozygous mutant embryos were identified during gestation, and in a separate study none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals.[15]

Interactions[edit]

HDAC3 has been shown to interact with:

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000171720 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024454 - Ensembl, May 2017
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Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.