Promoter chromatin remodeling of immediate-early genes is mediated through H3 phosphorylation at either serine 28 or 10 by the MSK1 multi-protein complex.
Promoter chromatin remodeling of immediate-early genes is mediated through H3 phosphorylation at either serine 28 or 10 by the MSK1 multi-protein complex.
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DOI：
10.1093/nar/gkq030
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发表时间：
2010-06
影响因子：
14.9
通讯作者：
Davie JR
中科院分区：
文献类型：
--
作者：
Drobic B;Pérez-Cadahía B;Yu J;Kung SK;Davie JR
当ERK和p38 MAPK途径激活时，MSK 1/2介导的核小体反应（包括H3在丝氨酸28或10处的磷酸化）与立即早期（IE）基因转录的诱导相结合。这种反应的结果随刺激和细胞环境而变化，范围从肿瘤转化到神经元突触可塑性。在这里，我们使用顺序免疫共沉淀试验和顺序染色质免疫沉淀（ChIP）试验对小鼠成纤维细胞10 T1/2和MSK 1敲低10 T1/2细胞显示，H3丝氨酸28和10磷酸化导致启动子重塑。MSK 1与磷酸丝氨酸接头14-3-3蛋白和SWI/SNF重塑物的ATP酶亚基BRG 1复合，通过转录因子如Elk-1或NF-κB募集到靶基因的启动子。在MSK 1介导的H3磷酸化后，BRG 1通过14-3-3蛋白与靶基因的启动子结合，这些蛋白充当支架。募集的SWI/SNF在IE基因的启动子处重塑核小体，使得能够结合转录因子如JUN并启动转录。
Upon activation of the ERK and p38 MAPK pathways, the MSK1/2-mediated nucleosomal response, including H3 phosphorylation at serine 28 or 10, is coupled with the induction of immediate-early (IE) gene transcription. The outcome of this response, varying with the stimuli and cellular contexts, ranges from neoplastic transformation to neuronal synaptic plasticity. Here, we used sequential co-immunoprecipitation assays and sequential chromatin immunoprecipitation (ChIP) assays on mouse fibroblast 10T1/2 and MSK1 knockdown 10T1/2 cells to show that H3 serine 28 and 10 phosphorylation leads to promoter remodeling. MSK1, in complexes with phospho-serine adaptor 14-3-3 proteins and BRG1 the ATPase subunit of the SWI/SNF remodeler, is recruited to the promoter of target genes by transcription factors such as Elk-1 or NF-κB. Following MSK1-mediated H3 phosphorylation, BRG1 associates with the promoter of target genes via 14-3-3 proteins, which act as scaffolds. The recruited SWI/SNF remodels nucleosomes at the promoter of IE genes enabling the binding of transcription factors like JUN and the onset of transcription.
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影响因子：
11.4
作者：
Beck, Ilse Me;Vanden Berghe, Wim;De Bosscher, Karolien
通讯作者：
De Bosscher, Karolien
影响因子：
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