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

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 functi on. Mutations in the hATRX gene cause severe syndromal mental retardation a ssociated with alpha-thalassemia, Using indirect immunofluorescence and con focal microscopy we have shown that ATRX protein is associated with pericen tromeric: heterochromatin during interphase and mitosis. By coimmunofluores cence, ATRX localizes with a mouse homologue of the Drosophila heterochroma tic protein HP1 in vivo, consistent with a previous two-hybrid screen ident ifying this interaction. From the analysis of a trap assay for nuclear prot eins, we have shown that the localization of ATRX to heterochromatin is enc oded 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. Th e unexpected association of a putative transcriptional regulator with highl y repetitive DNA provides a potential explanation for the variability in ph enotype of patients with identical mutations in the ATRX gene.