replication and active demethylation represent partially overlapping mechanisms for erasure of h3k4me3 in budding yeast复制和活跃的脱甲基代表部分重叠机制消除h3k4me3出芽酵母.pdfVIP

Replication and Active Demethylation Represent Partially Overlapping Mechanisms for Erasure of H3K4me3 in Budding Yeast 1. 1.¤ 2,3 4 1 Marta Radman-Livaja , Chih Long Liu , Nir Friedman , Stuart L. Schreiber , Oliver J. Rando * 1 Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America, 2 School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel, 3 The Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel, 4 Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America Abstract Histone modifications affect DNA–templated processes ranging from transcription to genomic replication. In this study, we examine the cell cycle dynamics of the trimethylated form of histone H3 lysine 4 (H3K4me3), a mark of active chromatin that is viewed as ‘‘long-lived’’ and that is involved in memory during cell state inheritance in metazoans. We synchronized yeast using two different protocols, then followed H3K4me3 patterns as yeast passed through subsequent cell cycles. While most H3K4me3 patterns were conserved from one generation to the next, we found that methylation patterns induced by alpha factor or high temperature were erased within one cell cycle, during S phase. Early-replicating regions were erased before late-replicating regions, implicating replication in H3K4me3 loss. However, nearly complete H3K4me3 erasure occurred at the majority of loci even when replication was prevented, suggesting that most erasure results from an active process. Indeed, deletion of the demethylase Jhd2 slowed erasure at