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Histone deacetylase 4, also known as HDAC4, is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''HDAC4''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.


Function

Histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...
s play a critical role in
transcriptional regulation In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from alt ...
,
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
progression, and developmental events. Histone
acetylation : In organic chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply '' acetates''. Deacetylation is the oppo ...
/deacetylation alters
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class II of the
histone deacetylase Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around his ...
/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly but through
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s
MEF2C 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. Genomics The gene is l ...
and
MEF2D Myocyte-specific enhancer factor 2D is a protein that in humans is encoded by the ''MEF2D'' gene. Interactions MEF2D has been shown to interact with: * CABIN1, * EP300, * MAPK7, * Myocyte-specific enhancer factor 2A, * NFATC2 * Sp1 transcri ...
. It seems to interact in a multiprotein complex with RbAp48 and HDAC3. Furthermore, HDAC4 is required for TGFbeta1-induced myofibroblastic differentiation.


Clinical significance

Studies have shown that HDAC4 regulates bone and muscle development.
Harvard University Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
researchers also concluded that it promotes healthy vision: Reduced levels of the protein led to the death of the rod photoreceptors and bipolar cells in the
retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...
s of mice.


Interactions

HDAC4 has been shown to
interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with: * BCL6, *
BTG2 Protein BTG2 also known as BTG family member 2 or NGF-inducible anti-proliferative protein PC3 or NGF-inducible protein TIS21, is a protein that in humans is encoded by the ''BTG2'' gene (B-cell translocation gene 2) and in other mammals by the ho ...
, * CBX5, *
GATA1 GATA-binding factor 1 or GATA-1 (also termed Erythroid transcription factor) is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by ...
, *
HDAC3 Histone deacetylase 3 is an enzyme encoded by the ''HDAC3'' gene in both humans and mice. Function Histones are highly alkaline proteins that package and order DNA into structural units called nucleosomes, which comprise the major protein comp ...
, *
MAPK1 Mitogen-activated protein kinase 1, (MAPK 1), also known as ERK2, is an enzyme that in humans is encoded by the ''MAPK1'' gene. Function The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracel ...
, *
MAPK3 Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the ''MAPK3'' gene. Function The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) famil ...
, *
MEF2C 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. Genomics The gene is l ...
, * Myocyte-specific enhancer factor 2A, *
Nuclear receptor co-repressor 1 The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the ''NCOR1'' gene. NCOR1 is a transcriptional coregulatory protein which c ...
, *
Nuclear receptor co-repressor 2 The nuclear receptor co-repressor 2 () is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists ...
, *
Testicular receptor 2 The testicular receptor 2 (TR2) also known as NR2C1 (nuclear receptor subfamily 2, group C, member 1) is protein that in humans is encoded by the ''NR2C1'' gene. TR2 is a member of the nuclear receptor family of transcription factors. Interactio ...
, *
YWHAB 14-3-3 protein beta/alpha is a protein that in humans is encoded by the ''YWHAB'' gene. Function This gene encodes a protein belonging to the 14-3-3 family of proteins, members of which mediate signal transduction by binding to phosphoserine-c ...
, *
YWHAE 14-3-3 protein epsilon is a protein that in humans is encoded by the ''YWHAE'' gene. Function This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This hi ...
, and *
Zinc finger and BTB domain-containing protein 16 Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ''ZBTB16'' gene. Function This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor ...
.


See also

*
Histone deacetylase Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around his ...


References


Further reading

* * * * * * * * * * * * * * * * * * *


External links

* {{Portal bar, Biology, border=no EC 3.5.1