Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes

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Item Type:	Article
Title:	Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes
Creators Name:	McDowell, T.L., Gibbons, R.J., Sutherland, H., O'Rourke, D.M., Bickmore, W.A., Pombo, A., Turley, H., Gatter, K., Picketts, D.J., Buckle, V.J., Chapman, L., Rhodes, D. and Higgs, D.R.
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 α-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.
Keywords:	COS Cells, Cell Fractionation, Centromere, Chromobox Protein Homolog 5, Chromosomes, DNA Helicases, DNA-Binding Proteins, HeLa Cells, Heterochromatin, Inbred BALB C Mice, Monoclonal Antibodies, Non-Histone Chromosomal Proteins, Nuclear Proteins, Transcription Factors, Transformed Cell Line, X-linked Nuclear Protein, Animals, Mice, Sheep
Source:	Proceedings of the National Academy of Sciences of the United States of America
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Volume:	96
Number:	24
Page Range:	13983-8
Date:	23 November 1999
Additional Information:	Copyright © 1999, The National Academy of Sciences.
Official Publication:	https://doi.org/10.1073/pnas.96.24.13983
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