Alpha-thalassemia mental retardation (ATR-X) syndrome: Elucidating cellular functions of the ATRX gene

Abstract

Mutations in the ATRX gene are responsible for the alpha-thalassemia mental retardation (ATR-X) syndrome. ATRX is a putative global transcription regulator and chromatin remodelling protein. The goal of this research is to characterize interactions ATRX has with other proteins involved in transcription regulation, and identify domains in ATRX that may be responsible for these interactions. Several stable NIH 3T3 tet-off cell lines have been established that contain a human ATRX transgene. In addition, ATRX, PML, and Daxx appear to co-localize in nuclear bundles, suggesting they may act together transiently, or in a complex, in a regulatory role. A domain has been identified on ATRX that appears to target the protein to nuclear bundles, and interact with PML and Daxx. ATRX patient mutations appear to alter these interactions. This work attempts to elucidate cellular functions of ATRX, in hopes of establishing a better understanding of the neuropathology of this complex disease.