Transcriptional regulator ATRX also known as ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein (XNP) 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 ''ATRX''
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
Transcriptional regulator ATRX contains an
ATPase
ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...
/
helicase
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...
domain, and thus it belongs to the
SWI/SNF
In molecular biology, SWI/SNF (SWItch/Sucrose Non-Fermentable), is a subfamily of ATP-dependent chromatin remodeling complexes, which is found in eukaryotes. In other words, it is a group of proteins that associate to remodel the way DNA is pack ...
family of
chromatin remodeling
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out ...
proteins. ATRX is required for deposition of the histone variant
H3.3 at
telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
s and other genomic repeats.
These interactions are important for maintaining silencing at these sites.
In addition, ATRX undergoes cell cycle-dependent phosphorylation, which regulates its nuclear matrix and chromatin association, and suggests its involvement in the gene regulation at interphase and chromosomal segregation in mitosis.
Clinical significance
Inherited mutations
Inherited mutations of the ATRX gene are associated with an X-linked mental retardation (
XLMR) syndrome most often accompanied by
alpha-thalassemia
Alpha-thalassemia (α-thalassemia, α-thalassaemia) is a form of thalassemia involving the genes '' HBA1'' and '' HBA2''. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule ...
(
ATR-X) syndrome. These mutations have been shown to cause diverse changes in the pattern of
DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
, which may provide a link between chromatin remodeling, DNA methylation, and gene expression in developmental processes. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. Female carriers may demonstrate skewed
X chromosome inactivation
X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a ...
.
Somatic mutations
Acquired mutations in ATRX have been reported in a number of human cancers including pancreatic neuroendocrine tumours,
gliomas,
astrocytomas,
osteosarcomas,
and malignant pheochromocytomas.
There is a strong correlation between ATRX mutations and an
Alternative Lengthening of Telomeres (ALT) phenotype in cancers.
Interactions
ATRX forms a complex with
DAXX
Death-associated protein 6 also known as Daxx is a protein that in humans is encoded by the ''DAXX'' gene.
Function
Daxx, a Death domain-associated protein, was first discovered through its cytoplasmic interaction with the classical death r ...
which is an histone H3.3 chaperone.
ATRX has been also 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
EZH2
Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme ( EC 2.1.1.43) encoded by gene, that participates in histone methylation and, ultimately, transcriptional repression. EZH2 catalyzes the addition of methyl groups ...
.
See also
*
Alpha-thalassemia mental retardation syndrome
Alpha-thalassemia mental retardation syndrome (ATRX), also called alpha-thalassemia X-linked intellectual disability syndrome, nondeletion type or ATR-X syndrome, is an X-linked recessive condition associated with a mutation in the ''ATRX'' gene. ...
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Alpha-Thalassemia X-Linked Mental Retardation Syndrome; ATRX Syndrome; Alpha Thalassemia/Mental Retardation, X-Linked; XLMR-Hypotonic Face Syndrome OMIM entries on Alpha-Thalassemia X-Linked Mental Retardation Syndrome*
* {{UCSC gene info, RAD54L