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, including 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 biological 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 chromosome breakage or segregation, it seems more likely that the XNP protein is somehow involved in regulation of gene expression. Recent genetic and biochemical studies have led to the emerging concept that SNF2-like proteins are components of a large protein complex which may exert its functions by modulating chromatin structure. To investigate whether 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 of these observations, we discuss how the XNP protein may regulate gene transcription at the chromatin level.
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Unit INSERM U406, Génétique Médicale et Développement, Faculté de Médecine de la Timone, 27 Boulevard Jean Moulin, 13385 Marseille cedex 05, France.
Timsit
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Villard
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Khrestchatisky
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Fontès
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Colleaux
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D000818:Animals; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000075924:X-linked Nuclear Protein; D016335:Zinc Fingers / Q000235:genetics; D001616:beta-Galactosidase / Q000378:metabolism
C069077:BMI1 protein, human; C489421:Bmi1 protein, mouse; C489420:Bmi1 protein, rat; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C489348:PCGF2 protein, human; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C083329:E(z) protein, Drosophila; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1; D001616:beta-Galactosidase; D004265:DNA Helicases; C092332:ATRX protein, human; C490462:Atrx protein, mouse; D000075924:X-linked Nuclear Protein