Requirement for PRC1 subunit BMI1 in host gene activation by Epstein-Barr virus protein EBNA3C.
Requirement for PRC1 subunit BMI1 in host gene activation by Epstein-Barr virus protein EBNA3C.
复制标题
Epstein-Barr 病毒蛋白 EBNA3C 激活宿主基因时需要 PRC1 亚基 BMI1。
DOI：
10.1093/nar/gky1323
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发表时间：
2019
影响因子：
14.9
通讯作者：
Paschos K
中科院分区：
文献类型：
--
作者：
Paschos K
EB病毒蛋白EBNA 3A、EBNA 3B和EBNA 3C在感染后控制数百个宿主基因。EBNA 3调节基因周围表观遗传标记的变化表明，它们与表观遗传因子合作发挥转录控制作用。多梳阻遏复合物（PRC）2亚基SUZ 12和PRC 1亚基BMI 1的作用进行了评估，其在EBNA 3介导的抑制和激活的重要性。进行SUZ 12和BMI 1的ChIP-seq实验以确定它们在染色质上的全局定位，并且分析提供了对分化细胞中多梳蛋白分布的进一步了解。将它们的定位与每个EBNA 3的定位进行比较，以解决关于EBNA 3-polycomb关系的长期问题。SUZ 12不与任何EBNA 3共定位，而EBNA 3C显著共定位并与BMI 1共免疫沉淀。在表达条件性EBNA 3C的细胞中，在EBNA 3C激活后，BMI 1被隔离到EBNA 3C结合位点。当SUZ 12或BMI 1在同一细胞中被敲低时，SUZ 12对EBNA 3C介导的调节没有贡献。令人惊讶的是，BMI 1敲低后，EBNA 3C同样有效地抑制，但EBNA 3C的宿主基因激活受损。这推翻了先前关于BMI 1/PRC 1在EBNA 3C介导的调控过程中功能的假设，首次直接鉴定了参与EBNA 3介导的激活的宿主因子，并为PRC 1如何参与基因激活提供了新的见解。
Epstein–Barr virus proteins EBNA3A, EBNA3B and EBNA3C control hundreds of host genes after infection. Changes in epigenetic marks around EBNA3-regulated genes suggest that they exert transcriptional control in collaboration with epigenetic factors. The roles of polycomb repressive complex (PRC)2 subunit SUZ12 and of PRC1 subunit BMI1 were assessed for their importance in EBNA3-mediated repression and activation. ChIP-seq experiments for SUZ12 and BMI1 were performed to determine their global localization on chromatin and analysis offered further insight into polycomb protein distribution in differentiated cells. Their localization was compared to that of each EBNA3 to resolve longstanding questions about the EBNA3–polycomb relationship. SUZ12 did not co-localize with any EBNA3, whereas EBNA3C co-localized significantly and co-immunoprecipitated with BMI1. In cells expressing a conditional EBNA3C, BMI1 was sequestered to EBNA3C-binding sites after EBNA3C activation. When SUZ12 or BMI1 was knocked down in the same cells, SUZ12 did not contribute to EBNA3C-mediated regulation. Surprisingly, after BMI1 knockdown, EBNA3C repressed equally efficiently but host gene activation by EBNA3C was impaired. This overturns previous assumptions about BMI1/PRC1 functions during EBNA3C-mediated regulation, for the first time identifies directly a host factor involved in EBNA3-mediated activation and provides a new insight into how PRC1 can be involved in gene activation.