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.[1][2][3]
Function
Transcriptional regulator ATRX contains an ATPase / helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins. This protein is found to undergo 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.[3]
Clinical significance
Mutations of the ATRX gene are associated with an X-linked mental retardation (XLMR) syndrome most often accompanied by alpha-thalassemia (ATRX) 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.[3]
Interactions
ATRX has been shown to interact with EZH2.[4]
See also
References
- ↑ Stayton CL, Dabovic B, Gulisano M, Gecz J, Broccoli V, Giovanazzi S et al. (April 1995). "Cloning and characterization of a new human Xq13 gene, encoding a putative helicase". Hum Mol Genet 3 (11): 1957–64. doi:10.1093/hmg/3.11.1957. PMID 7874112.
- ↑ Gibbons RJ, Suthers GK, Wilkie AO, Buckle VJ, Higgs DR (November 1992). "X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis". Am J Hum Genet 51 (5): 1136–49. PMC 1682840. PMID 1415255.
- ↑ 3.0 3.1 3.2 "Entrez Gene: ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae)".
- ↑ Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L (1998). "Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein". Hum. Mol. Genet. 7 (4): 679–84. doi:10.1093/hmg/7.4.679. PMID 9499421.
Further reading
- Mulley JC, Kerr B, Stevenson R, Lubs H (1992). "Nomenclature guidelines for X-linked mental retardation". Am. J. Med. Genet. 43 (1–2): 383–91. doi:10.1002/ajmg.1320430159. PMID 1605216.
- Tang P, Park DJ, Marshall Graves JA, Harley VR (2005). "ATRX and sex differentiation". Trends Endocrinol. Metab. 15 (7): 339–44. doi:10.1016/j.tem.2004.07.006. PMID 15350606.
- Forget BG (2006). "De novo and acquired forms of alpha thalassemia". Curr. Hematol. Rep. 5 (1): 11–4. PMID 16537041.
- Adès LC, Kerr B, Turner G, Wise G (1992). "Smith-Fineman-Myers syndrome in two brothers". Am. J. Med. Genet. 40 (4): 467–70. doi:10.1002/ajmg.1320400419. PMID 1684092.
- 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)". Am. J. Med. Genet. 30 (1–2): 493–508. doi:10.1002/ajmg.1320300152. PMID 3177467.
- Shapiro MB, Senapathy P (1987). "RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression". Nucleic Acids Res. 15 (17): 7155–74. doi:10.1093/nar/15.17.7155. PMC 306199. PMID 3658675.
- Gibbons RJ, Picketts DJ, Villard L, Higgs DR (1995). "Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome)". Cell 80 (6): 837–45. doi:10.1016/0092-8674(95)90287-2. PMID 7697714.
- Wang LH, Collins A, Lawrence S, Keats BJ, Morton NE (1995). "Integration of gene maps: chromosome X". Genomics 22 (3): 590–604. doi:10.1006/geno.1994.1432. PMID 8001970.
- Gecz J, Pollard H, Consalez G, Villard L, Stayton C, Millasseau P et al. (1994). "Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3". Hum. Mol. Genet. 3 (1): 39–44. doi:10.1093/hmg/3.1.39. PMID 8162050.
- Villard L, Gecz J, Mattéi JF, Fontés M, Saugier-Veber P, Munnich A et al. (1996). "XNP mutation in a large family with Juberg-Marsidi syndrome". Nat. Genet. 12 (4): 359–60. doi:10.1038/ng0496-359. PMID 8630485.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Picketts DJ, Higgs DR, Bachoo S, Blake DJ, Quarrell OW, Gibbons RJ (1997). "ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome". Hum. Mol. Genet. 5 (12): 1899–907. doi:10.1093/hmg/5.12.1899. 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". Eur. J. Hum. Genet. 4 (6): 316–20. PMID 9043863.
- Villard L, Lossi AM, Cardoso C, Proud V, Chiaroni P, Colleaux L et al. (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. PMID 9244431.
- Golub EI, Kovalenko OV, Gupta RC, Ward DC, Radding CM (1997). "Interaction of human recombination proteins Rad51 and Rad54". Nucleic Acids Res. 25 (20): 4106–10. doi:10.1093/nar/25.20.4106. PMC 147015. PMID 9321665.
- Gibbons RJ, Bachoo S, Picketts DJ, Aftimos S, Asenbauer B, Bergoffen J et al. (1997). "Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain". Nat. Genet. 17 (2): 146–8. doi:10.1038/ng1097-146. PMID 9326931.
- Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L (1998). "Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein". Hum. Mol. Genet. 7 (4): 679–84. doi:10.1093/hmg/7.4.679. PMID 9499421.
- Bérubé NG, Mangelsdorf M, Jagla M, Vanderluit J, Garrick D, Gibbons RJ et al. (2005). "The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis". J. Clin. Invest. 115 (2): 258–267. doi:10.1172/JCI200522329. PMC 544602. PMID 15668733.