title: Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes.
abstract: ATRX is a member of the SNF2 family of helicase/ATPases that is thought to regulate gene expression via an effect on chromatin structure and/or function. Mutations in the hATRX gene cause severe syndromal mental retardation associated with alpha-thalassemia. Using indirect immunofluorescence and confocal microscopy we have shown that ATRX protein is associated with pericentromeric heterochromatin during interphase and mitosis. By coimmunofluorescence, ATRX localizes with a mouse homologue of the Drosophila heterochromatic protein HP1 in vivo, consistent with a previous two-hybrid screen identifying this interaction. From the analysis of a trap assay for nuclear proteins, we have shown that the localization of ATRX to heterochromatin is encoded by its N-terminal region, which contains a conserved plant homeodomain-like finger and a coiled-coil domain. In addition to its association with heterochromatin, at metaphase ATRX clearly binds to the short arms of human acrocentric chromosomes, where the arrays of ribosomal DNA are located. The unexpected association of a putative transcriptional regulator with highly repetitive DNA provides a potential explanation for the variability in phenotype of patients with identical mutations in the ATRX gene.
authors.affiliation: Medical Research Council Molecular Haematology Unit, Institute of Molecular Medicine, Oxford OX3 9DS, United Kingdom.
authors.forename: T L
authors.initials: TL
authors.lastname: McDowell
authors.forename: R J
authors.initials: RJ
authors.lastname: Gibbons
authors.forename: H
authors.initials: H
authors.lastname: Sutherland
authors.forename: D M
authors.initials: DM
authors.lastname: O'Rourke
authors.forename: W A
authors.initials: WA
authors.lastname: Bickmore
authors.forename: A
authors.initials: A
authors.lastname: Pombo
authors.forename: H
authors.initials: H
authors.lastname: Turley
authors.forename: K
authors.initials: K
authors.lastname: Gatter
authors.forename: D J
authors.initials: DJ
authors.lastname: Picketts
authors.forename: V J
authors.initials: VJ
authors.lastname: Buckle
authors.forename: L
authors.initials: L
authors.lastname: Chapman
authors.forename: D
authors.initials: D
authors.lastname: Rhodes
authors.forename: D R
authors.initials: DR
authors.lastname: Higgs
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D019556:COS Cells; D002458:Cell Fractionation; D002461:Cell Line, Transformed; D002503:Centromere / Q000737:chemistry*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002875:Chromosomes / Q000737:chemistry; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D006570:Heterochromatin / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D012756:Sheep; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D000075924:X-linked Nuclear Protein
chemical_list: D000911:Antibodies, Monoclonal; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D009687:Nuclear Proteins; D014157:Transcription Factors; D000090266:Chromobox Protein Homolog 5; D004265:DNA Helicases; C092332:ATRX protein, human; C490462:Atrx protein, mouse; D000075924:X-linked Nuclear Protein