Multiple roles of H2A.Z in regulating promoter chromatin architecture in human cells.
Multiple roles of H2A.Z in regulating promoter chromatin architecture in human cells.
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DOI：
10.1038/s41467-021-22688-x
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发表时间：
2021-05-05
影响因子：
16.6
通讯作者：
Tremethick DJ
中科院分区：
文献类型：
--
作者：
Cole L;Kurscheid S;Nekrasov M;Domaschenz R;Vera DL;Dennis JH;Tremethick DJ
启动子的染色质可及性是调节转录活性的基础。组蛋白变体 H2A.Z 已被证明有助于这种调节，但其作用仍然知之甚少。在这里，我们为上皮、间充质和同基因癌细胞系中的所有人类 Pol II 启动子准备了含有 H2A.Z 的核小体的位置和可及性的高深度图。我们发现，与流行的模型相反，观察到许多不同类型的活性和非活性启动子结构，它们的核小体组织和对 MNase 消化的敏感性不同。活性染色质结构的关键方面包括位于 TSS 上游或下游的 H2A.Z MNase 抗性核小体，以及 TSS 处的 MNase 敏感核小体。此外，H2A.Z 的缺失导致转录因子结合位点的可及性显着增加。总的来说，这些结果表明 H2A.Z 在调节基因表达方面具有多种不同的作用，具体取决于其在启动子中的位置。组蛋白变体 H2A.Z 被认为有助于启动子可及性的调节。在这里，作者展示了人类 Pol II 启动子中含有 H2A.Z 的核小体的位置和可及性的高深度图，并提供了证据，证明 H2A.Z 在调节基因表达方面具有多种不同的作用，具体取决于其在启动子中的位置。
Chromatin accessibility of a promoter is fundamental in regulating transcriptional activity. The histone variant H2A.Z has been shown to contribute to this regulation, but its role has remained poorly understood. Here, we prepare high-depth maps of the position and accessibility of H2A.Z-containing nucleosomes for all human Pol II promoters in epithelial, mesenchymal and isogenic cancer cell lines. We find that, in contrast to the prevailing model, many different types of active and inactive promoter structures are observed that differ in their nucleosome organization and sensitivity to MNase digestion. Key aspects of an active chromatin structure include positioned H2A.Z MNase resistant nucleosomes upstream or downstream of the TSS, and a MNase sensitive nucleosome at the TSS. Furthermore, the loss of H2A.Z leads to a dramatic increase in the accessibility of transcription factor binding sites. Collectively, these results suggest that H2A.Z has multiple and distinct roles in regulating gene expression dependent upon its location in a promoter. Histone variant H2A.Z has been suggested to contribute to the regulation of promoter accessibility. Here, the authors present high-depth maps of the position and accessibility of H2A.Z-containing nucleosomes for human Pol II promoters and provide evidence that H2A.Z has multiple and distinct roles in regulating gene expression dependent upon its location in a promoter.
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