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 ATRXgene.[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 intellectual disability (XLMR) syndrome most often accompanied by alpha-thalassemia (ATR-X) syndrome. These mutations have been shown to cause diverse changes in the pattern of DNA methylation, 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.[7]
↑"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.
↑Stayton CL, Dabovic B, Gulisano M, Gecz J, Broccoli V, Giovanazzi S, etal. (November 1994). "Cloning and characterization of a new human Xq13 gene, encoding a putative helicase". Human Molecular Genetics. 3 (11): 1957–64. doi:10.1093/hmg/3.11.1957. PMID7874112.
↑Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, etal. (January 2012). "Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma". Nature. 482 (7384): 226–31. Bibcode:2012Natur.482..226S. doi:10.1038/nature10833. PMID22286061. S2CID4312169.
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. doi:10.1002/ajmg.1320430159. PMID1605216.
Tang P, Park DJ, Marshall Graves JA, Harley VR (September 2004). "ATRX and sex differentiation". Trends in Endocrinology and Metabolism. 15 (7): 339–44. doi:10.1016/j.tem.2004.07.006. PMID15350606. S2CID22192941.
Forget BG (March 2006). "De novo and acquired forms of alpha thalassemia". Current Hematology Reports. 5 (1): 11–4. PMID16537041.
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. doi:10.1002/ajmg.1320400419. PMID1684092.
Sutherland GR, Gedeon AK, Haan EA, Woodroffe P, Mulley JC (1988). "Linkage studies with the gene for an X-linked syndrome of mental retardation, microcephaly and spastic diplegia (MRX2)". American Journal of Medical Genetics. 30 (1–2): 493–508. doi:10.1002/ajmg.1320300152. PMID3177467.
Wang LH, Collins A, Lawrence S, Keats BJ, Morton NE (August 1994). "Integration of gene maps: chromosome X". Genomics. 22 (3): 590–604. doi:10.1006/geno.1994.1432. PMID8001970.
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. doi:10.1093/hmg/3.1.39. PMID8162050.
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. doi:10.1038/ng0496-359. PMID8630485. S2CID33759894.
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. doi:10.1159/000472225. PMID9043863. S2CID43618843.
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. doi:10.1006/geno.1997.4793. PMID9244431.
