ATRX
Transcriptional regulator ATRX also known as ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein (XNP) is a protein that in humans is encoded by the ATRX gene.[5][6][7]
Function
Transcriptional regulator ATRX contains an ATPase / helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins. ATRX is required for deposition of the histone variant H3.3 at telomeres and other genomic repeats.[8] These interactions are important for maintaining silencing at these sites.[9][10][11]
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.[7]
Clinical significance
Inherited mutations
Inherited mutations of the ATRX gene are associated with an X-linked mental retardation (
X chromosome inactivation.[7]
Somatic mutations
Acquired mutations in ATRX have been reported in a number of human cancers including pancreatic neuroendocrine tumours,[12] gliomas,[13] [14] osteosarcomas,[15] soft-tissue sarcomas,[16] and malignant pheochromocytomas.[17] There is a strong correlation between ATRX mutations and an Alternative Lengthening of Telomeres (ALT) phenotype in cancers.[12]
Interactions
ATRX forms a complex with
DAXX which is an histone H3.3 chaperone.[18]
ATRX has been also shown to
See also
- Alpha-thalassemia mental retardation syndrome
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000085224 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031229 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 7874112.
- PMID 1415255.
- ^ a b c "Entrez Gene: ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae)".
- PMID 20110566.
- PMID 25865896.
- PMID 25938714.
- PMID 26304540.
- ^ PMID 21719641.
- S2CID 4312169.
- PMID 23104868.
- PMID 24703847.
- PMID 29100075.
- PMID 27209355.
- PMID 20651253.
- PMID 9499421.
Further reading
- Mulley JC, Kerr B, Stevenson R, Lubs H (1992). "Nomenclature guidelines for X-linked mental retardation". American Journal of Medical Genetics. 43 (1–2): 383–91. PMID 1605216.
- Tang P, Park DJ, Marshall Graves JA, Harley VR (September 2004). "ATRX and sex differentiation". Trends in Endocrinology and Metabolism. 15 (7): 339–44. S2CID 22192941.
- Forget BG (March 2006). "De novo and acquired forms of alpha thalassemia". Current Hematology Reports. 5 (1): 11–4. PMID 16537041.
- Adès LC, Kerr B, Turner G, Wise G (September 1991). "Smith-Fineman-Myers syndrome in two brothers". American Journal of Medical Genetics. 40 (4): 467–70. PMID 1684092.
- PMID 3177467.
- Shapiro MB, Senapathy P (September 1987). "RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression". Nucleic Acids Research. 15 (17): 7155–74. PMID 3658675.
- Gibbons RJ, Picketts DJ, Villard L, Higgs DR (March 1995). "Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome)". Cell. 80 (6): 837–45. PMID 7697714.
- Wang LH, Collins A, Lawrence S, Keats BJ, Morton NE (August 1994). "Integration of gene maps: chromosome X". Genomics. 22 (3): 590–604. PMID 8001970.
- Gecz J, Pollard H, Consalez G, Villard L, Stayton C, Millasseau P, Khrestchatisky M, Fontes M (January 1994). "Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3". Human Molecular Genetics. 3 (1): 39–44. PMID 8162050.
- Villard L, Gecz J, Mattéi JF, Fontés M, Saugier-Veber P, Munnich A, Lyonnet S (April 1996). "XNP mutation in a large family with Juberg-Marsidi syndrome". Nature Genetics. 12 (4): 359–60. S2CID 33759894.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. PMID 8889548.
- Picketts DJ, Higgs DR, Bachoo S, Blake DJ, Quarrell OW, Gibbons RJ (December 1996). "ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome". Human Molecular Genetics. 5 (12): 1899–907. PMID 8968741.
- Villard L, Lacombe D, Fontés M (1997). "A point mutation in the XNP gene, associated with an ATR-X phenotype without alpha-thalassemia". European Journal of Human Genetics. 4 (6): 316–20. S2CID 43618843.
- Villard L, Lossi AM, Cardoso C, Proud V, Chiaroni P, Colleaux L, Schwartz C, Fontés M (July 1997). "Determination of the genomic structure of the XNP/ATRX gene encoding a potential zinc finger helicase". Genomics. 43 (2): 149–55. PMID 9244431.
- Golub EI, Kovalenko OV, Gupta RC, Ward DC, Radding CM (October 1997). "Interaction of human recombination proteins Rad51 and Rad54". Nucleic Acids Research. 25 (20): 4106–10. PMID 9321665.
- Gibbons RJ, Bachoo S, Picketts DJ, Aftimos S, Asenbauer B, Bergoffen J, Berry SA, Dahl N, Fryer A, Keppler K, Kurosawa K, Levin ML, Masuno M, Neri G, Pierpont ME, Slaney SF, Higgs DR (October 1997). "Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain". Nature Genetics. 17 (2): 146–8. S2CID 12470300.
- Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L (April 1998). "Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein". Human Molecular Genetics. 7 (4): 679–84. PMID 9499421.
- Bérubé NG, Mangelsdorf M, Jagla M, Vanderluit J, Garrick D, Gibbons RJ, Higgs DR, Slack RS, Picketts DJ (February 2005). "The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis". The Journal of Clinical Investigation. 115 (2): 258–67. PMID 15668733.
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
- Human ATRX genome location and ATRX gene details page in the UCSC Genome Browser.
- Human RAD54L genome location and RAD54L gene details page in the UCSC Genome Browser.