gene reactivation by 5-aza-2′-deoxycytidine–induced demethylation requires srcap–mediated h2a.z insertion to establish nucleosome depleted regions基因活化的5-aza-2u2032-deoxycytidine-induced脱甲基作用需要srcap-mediated h2a。.pdfVIP

Gene Reactivation by 5-Aza-29-Deoxycytidine–Induced Demethylation Requires SRCAP–Mediated H2A.Z Insertion to Establish Nucleosome Depleted Regions 1 2 1,3 1 1 Xiaojing Yang , Houtan Noushmehr , Han Han , Claudia Andreu-Vieyra , Gangning Liang , Peter A. Jones1* 1 Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America, 2 USC Epigenome Center, University of Southern California, Los Angeles, California, United States of America, 3 Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, United States of America Abstract 5-Aza-29-deoxycytidine, approved by the FDA for the treatment of myelodysplastic syndrome (MDS), is incorporated into the DNA of dividing cells where it specifically inhibits DNA methylation by forming covalent complexes with the DNA methyltransferases (DNMTs). In an effort to study the correlations between DNA methylation, nucleosome remodeling, and gene reactivation, we investigate the integrated epigenetic events that worked coordinately to reprogram the methylated and closed promoters back to permissive chromatin configurations after 5-Aza-29-deoxycytidine treatment. The ChIP results indicate that H2A.Z is deposited at promoter regions by the Snf2-related CBP activator protein (SRCAP) complex following DNA demethylation. According to our genome-wide expression and DNA methylation profiles, we find that the complete re-activation of silenced genes requires the insertion of the histone variant H2A.Z, which facilitates the acquisition of regions fully depleted of nucleosome as demonstrated by NO