Dynamics of polycomb proteins-mediated histone modifications during UV irradiation-induced DNA damage
Dynamics of polycomb proteins-mediated histone modifications during UV irradiation-induced DNA damage
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DOI：
10.1016/j.ibmb.2014.10.001
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发表时间：
2014-12-01
影响因子：
3.8
通讯作者：
Kusakabe, Takahiro
中科院分区：
文献类型：
--
作者：
Li, Zhiqing;Mon, Hiroaki;Kusakabe, Takahiro
已知多梳族 (PcG) 复合物是染色质修饰剂和转录阻遏蛋白。在这项工作中，我们报道了组蛋白修饰 PcG 复合物能够参与家蚕 Bombyx mori 中紫外线 (UV) 诱导的 DNA 损伤的修复过程。 PcG 基因缺失的蚕细胞对 UV-C 照射高度敏感，并且对细胞增殖的抑制作用增强。有趣的是，这里合成的蚕-人嵌合H2A蛋白中的SQ位点在UV-C照射下迅速磷酸化，这可以用作监测蚕细胞中DNA损伤反应的标记物。在这些 UV-C 照射条件下，我们发现 PRC1 介导的 H2AX 泛素化（而非 H2AZ）减少，并且这种去泛素化与其磷酸化事件无关。相比之下，UV-C 照射诱导组蛋白 H3 (H3K27me3) 上赖氨酸 27 的三甲基化增加，这是由另一个 PcG 亚复合物 PRC2 催化的转录沉默染色质的标志。总的来说，我们提供了关于家蚕响应 UV-C 损伤的染色质重塑的第一个证据，并揭示了 PcG 复合物介导的组蛋白修饰在有助于创建开放染色质结构以有效修复 DNA 损伤方面的另一层作用。 (C) 2014 Elsevier Ltd. 保留所有权利。
Polycomb group (PcG) complexes are known to be chromatin modifiers and transcriptional repressors. In this work, we reported that the histone-modifying PcG complexes are able to participate in the repair process of ultraviolet (UV)-induced DNA lesions in the silkworm, Bombyx mori. The silkworm cells with depletion of PcG genes showed hypersensitive to UV-C irradiation and increased inhibition of cell proliferation. Interestingly, an SQ site in the silkworm-human chimeric H2A protein synthesized here was phosphorylated rapidly upon UV-C exposure, which could be used as a marker for monitoring the response to DNA damage in silkworm cells. Under these UV-C irradiated conditions, we found that PRC1-mediated ubiquitylation of H2AX, but not of H2AZ, were decreased and this deubiquitylation was independent of its phosphorylation event. In contrast, UV-C irradiation induced the increase of trimethylation of lysine 27 on histone H3 (H3K27me3), a mark of transcriptionally silent chromatin catalyzed by another PcG subcomplex, PRC2. Collectively, we provided the first evidence on chromatin remodeling in response to UV-C lesion in silkworm and revealed another layer role for PcG complexes-mediated histone modifications in contributing to creating an open chromatin structure for the efficient repair of DNA damages. (C) 2014 Elsevier Ltd. All rights reserved.