有丝分裂期间 H2A.Z 的维持揭示了有丝分裂沉默基因上核小体的移位。
H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes.
机构信息
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
出版信息
Mol Cell. 2010 Sep 24;39(6):901-11. doi: 10.1016/j.molcel.2010.08.026.
Abstract
Profound chromatin changes occur during mitosis to allow for gene silencing and chromosome segregation followed by reactivation of memorized transcription states in daughter cells. Using genome-wide sequencing, we found H2A.Z-containing +1 nucleosomes of active genes shift upstream to occupy TSSs during mitosis, significantly reducing nucleosome-depleted regions. Single-molecule analysis confirmed nucleosome shifting and demonstrated that mitotic shifting is specific to active genes that are silenced during mitosis and, thus, is not seen on promoters, which are silenced by methylation or mitotically expressed genes. Using the GRP78 promoter as a model, we found H3K4 trimethylation is also maintained while other indicators of active chromatin are lost and expression is decreased. These key changes provide a potential mechanism for rapid silencing and reactivation of genes during the cell cycle.
摘要
在有丝分裂过程中会发生深刻的染色质变化，以允许基因沉默和染色体分离，随后在子细胞中重新激活记忆转录状态。使用全基因组测序，我们发现含有 H2A.Z 的 +1 核小体在有丝分裂过程中向转录起始位点上游移动，从而显著减少核小体缺失区域。单分子分析证实了核小体的移动，并表明有丝分裂中的移动是特定于在有丝分裂过程中沉默的活性基因的，因此在启动子上看不到这种现象，启动子被甲基化或有丝分裂表达的基因沉默。使用 GRP78 启动子作为模型，我们发现 H3K4 三甲基化也得以维持，而其他活性染色质的标志物则丢失，表达也降低。这些关键变化为细胞周期中基因的快速沉默和重新激活提供了潜在的机制。
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