Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics
Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics
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DOI：
10.1038/nsmb.2424
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发表时间：
2012-11-01
影响因子：
16.8
通讯作者：
Tremethick, David J.
中科院分区：
文献类型：
--
作者：
Nekrasov, Maxim;Amrichova, Jana;Tremethick, David J.
尽管已经明确确定，位于活性哺乳动物基因转录起始位点 (TSS) 的核小体耗尽区 (NDR) 侧翼的含有组蛋白 H2A.Z 的核小体，但这种基于染色质的信息如何通过细胞周期传递尚不清楚。我们在此表明，在小鼠滋养层干细胞中，启动子处的组蛋白 H2A.Z 量在 S 期期间减少，与 TSS 侧翼的同型 (H2A.Z-H2A.Z) 核小体变为异型 (H2A.Z-H2A) 一致。令我们惊讶的是，这些核小体在 M 期仍保持异型。在 TSS 中，我们发现了一个不稳定的异型组蛋白 H2A.Z，其包含 G1 期的核小体，该核小体在 DNA 复制后丢失。 TSS 的这些动态变化反映了 S 期和 M 期 NDR 的全局扩展，出乎意料的是，这与转录活性无关。与启动子处组蛋白 H2A.Z 的丢失同时发生，当有丝分裂开始时，组蛋白 H2A.Z 靶向着丝粒。
Although it has been clearly established that well-positioned histone H2A.Z-containing nucleosomes flank the nucleosome-depleted region (NDR) at the transcriptional start site (TSS) of active mammalian genes, how this chromatin-based information is transmitted through the cell cycle is unknown. We show here that in mouse trophoblast stem cells, the amount of histone H2A.Z at promoters decreased during S phase, coinciding with homotypic (H2A.Z-H2A.Z) nucleosomes flanking the TSS becoming heterotypic (H2A.Z-H2A). To our surprise these nucleosomes remained heterotypic at M phase. At the TSS, we identified an unstable heterotypic histone H2A.Z-containing nucleosome in G1 phase that was lost after DNA replication. These dynamic changes at the TSS mirror a global expansion of the NDR at S and M phases, which, unexpectedly, is unrelated to transcriptional activity. Coincident with the loss of histone H2A.Z at promoters, histone H2A.Z is targeted to the centromere when mitosis begins.