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首页> 外文期刊>Epigenetics & Chromatin >Menin and RNF20 recruitment is associated with dynamic histone modifications that regulate signal transducer and activator of transcription 1 (STAT1)-activated transcription of the interferon regulatory factor 1 gene (IRF1)
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Menin and RNF20 recruitment is associated with dynamic histone modifications that regulate signal transducer and activator of transcription 1 (STAT1)-activated transcription of the interferon regulatory factor 1 gene (IRF1)

机译：Menin和RNF20募集与动态组蛋白修饰有关，该修饰可调节信号转导子和转录激活因子1（STAT1）激活的干扰素调节因子1基因（IRF1）的转录

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Background Signal transducer and activator of transcription (STAT) activation of gene expression is both rapid and transient, and when properly executed it affects growth, differentiation, homeostasis and the immune response, but when dysregulated it contributes to human disease. Transcriptional activation is regulated by alterations to the chromatin template. However, the role of histone modification at gene loci that are activated for transcription in response to STAT signaling is poorly defined. Results Using chromatin immunoprecipitation, we profiled several histone modifications during STAT1 activation of the interferon regulatory factor 1 gene (IRF1). Methylated lysine histone proteins H3K4me2, H3K4me3, H3K79me3, H3K36me3 and monoubiquitinated histone ubH2B are dynamic and correlate with interferon (IFN)γ induction of STAT1 activity. Chemical inhibition of H3K4 methylation downregulates IRF1 transcription and decreases RNA polymerase II (Pol II) occupancy at the IRF1 promoter. MEN1, a component of a complex proteins associated with Set1 (COMPASS)-like complex and the hBRE1 component, RNF20, are localized to IRF1 in the uninduced state and are further recruited when IRF1 is activated. RNAi-mediated depletion of RNF20 lowers both ubH2B and H3K4me3, but surprisingly, upregulates IFNγ induced IRF1 transcription. The dynamics of phosphorylation in the C-terminal domain (CTD) of Pol II are disrupted during gene activation as well. Conclusions H2B monoubiquitination promotes H3K4 methylation, but the E3 ubiquitin ligase, RNF20, is repressive of inducible transcription at the IRF1 gene locus, suggesting that ubH2B can, directly or indirectly, affect Pol II CTD phosphorylation cycling to exert control on ongoing transcription.
机译：背景技术基因表达的信号转导子和转录激活子（STAT）的激活既快速又短暂，当正确执行时，它会影响生长，分化，体内平衡和免疫反应，但失调会导致人类疾病。转录激活通过染色质模板的改变来调节。但是，组蛋白修饰在基因位点的作用不明确，该基因位点被激活以响应STAT信号而转录。结果使用染色质免疫沉淀，我们在干扰素调节因子1基因（IRF1）的STAT1激活过程中描述了几种组蛋白修饰。甲基化赖氨酸组蛋白H3K4me2，H3K4me3，H3K79me3，H3K36me3和单泛素化组蛋白ubH2B是动态的，与干扰素（IFN）γ诱导的STAT1活性相关。化学抑制H3K4甲基化可下调IRF1转录并降低IRF1启动子上的RNA聚合酶II（Pol II）占有率。 MEN1是与Set1（COMPASS）样复合物相关的复合蛋白的一种成分，而hBRE1成分RNF20则以未诱导状态定位于IRF1，并在IRF1激活时进一步募集。 RNAi介导的RNF20耗竭降低了ubH2B和H3K4me3，但令人惊讶的是，上调了IFNγ诱导的IRF1转录。在基因激活过程中，Pol II的C末端结构域（CTD）中的磷酸化动力学也被破坏。结论H2B单泛素化促进H3K4甲基化，但E3泛素连接酶RNF20抑制IRF1基因位点的诱导转录，这表明ubH2B可以直接或间接影响Pol II CTD磷酸化循环，以控制正在进行的转录。

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