Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
PLoS Genet. 2010 Feb 5;6(2):e1000837. doi: 10.1371/journal.pgen.1000837.
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 most loci. Together, these results indicate overlapping roles for passive dilution and active enzymatic demethylation in erasing ancestral histone methylation states in yeast.
组蛋白修饰影响 DNA 模板的过程，范围从转录到基因组复制。在这项研究中，我们研究了组蛋白 H3 赖氨酸 4 三甲基化形式（H3K4me3）的细胞周期动态，H3K4me3 是活跃染色质的标志，被认为是“长寿的”，并且在后生动物细胞状态遗传过程中的记忆中发挥作用。我们使用两种不同的方案对酵母进行同步化，然后在酵母通过随后的细胞周期时跟踪 H3K4me3 模式。虽然大多数 H3K4me3 模式在下一个世代中是保守的，但我们发现由α因子或高温诱导的甲基化模式在 S 期内的一个细胞周期内被消除。早期复制区域在晚期复制区域之前被消除，暗示复制在 H3K4me3 丢失中起作用。然而，即使在阻止复制的情况下，大多数位点仍几乎完全消除了 H3K4me3，这表明大多数消除是由一个主动过程导致的。事实上，去甲基酶 Jhd2 的缺失会减缓大多数位点的消除。总之，这些结果表明，在酵母中，被动稀释和主动酶去甲基化在消除祖先组蛋白甲基化状态方面具有重叠作用。
