SPECIFIC INTERACTION BETWEEN THE XNP ATR-X GENE-PRODUCT AND THE SET DOMAIN OF THE HUMAN EZH2 PROTEIN/

Mutations in the XNP gene result in different inherited disorders, inc luding the ATR-X syndrome which is characterized by mental retardation (MR) associated with alpha-thalaessemia, Amino acid sequence analysis revealed that the XNP protein is a new member of the SNF2-like family , which comprises numerous members involved in a broad range of biolog ical functions: transcriptional regulation, DNA repair and chromosome segregation, Since experiments on fibroblasts from ATR-X patients have provided no evidence for either a DNA repair defect or abnormal chrom osome breakage or segregation, it seems more likely that the XNP prote in is somehow involved in regulation of gene expression, Recent geneti c and biochemical studies have led to the emerging concept that SNF2-l ike proteins are components of a large protein complex which may exert its functions by modulating chromatin structure, To investigate wheth er XNP could mediate the activity of gene-specific activators through chromatin remodelling, we performed a yeast two-hybrid analysis using XNP and several human heterochromatin-associated proteins. We found a specific interaction between the XNP and the EZH2 proteins, In light o f these observations, we discuss how the XNP protein may regulate gene transcription at the chromatin level.