H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes.
H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes.
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DOI：
10.1016/j.molcel.2010.08.026
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发表时间：
2010-09-24
期刊：
影响因子：
16
通讯作者：
Jones PA
中科院分区：
文献类型：
--
作者：
Kelly TK;Miranda TB;Liang G;Berman BP;Lin JC;Tanay A;Jones PA
在有丝分裂期间发生深刻的染色质变化，以允许基因沉默和染色体分离，随后子细胞中记忆的转录状态重新激活。使用全基因组测序，我们发现含有活性基因的+1核小体的H2A.Z在有丝分裂期间向上游移动以占据TSS，显著减少核小体耗尽区域。单分子分析证实了核小体移位，并证明有丝分裂移位是特异性的有丝分裂过程中沉默的活性基因，因此在启动子上看不到，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H3K4三甲基化也被维持，而其他活性染色质的指标丢失，表达降低。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机制。
Profound chromatin changes occur during mitosis to allow for gene silencing and chromosome segregation followed by re-activation 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 tri-methylation 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 re-activation of genes during the cell cycle.
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影响因子：
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