Polycomb chromobox(CBX)proteins regulate gene transcription by maintaining chromatin states,which guide a variety of biological processes.Now,epigenetic regulation of innate immune response is an emerging field.Howeve...Polycomb chromobox(CBX)proteins regulate gene transcription by maintaining chromatin states,which guide a variety of biological processes.Now,epigenetic regulation of innate immune response is an emerging field.However,the role of CBX proteins in innate immunity remains unclear.We confirmed that the expression of CBX family proteins,especially Cbx2,was decreased in macrophages upon viral infection,and then we investigated the role of Cbx2 in the antiviral immune response.Silencing or knockdown of Cbx2 in macrophages inhibited virus-induced production of IFNp.Furthermore,heterozygous Cbx2 knockout were susceptible to VSV challenge.Mechanistically,Cbx2 binds to and recruits Jmjd3 to the Ifnb promoter,leading to demethylation of H3K27me3 and increased transcription of IFN-β.Together,our study reveals a nontraditional function of a Cbx protein and adds new insight into the epigenetic regulation of antiviral innate immunity.展开更多
文摘Polycomb group complex (PcG)作为发挥转录抑制作用的重要表观遗传调控复合物参与发育、衰老以及肿瘤发生等重要生理过程。Pc G家族成员,包括PRC1 (Polycomb repressive complex 1)与PRC2 (Polycomb repressive complex 2)两种复合物,各组分间功能既协同,又不失特性,色素框同源蛋白(Chromobox homolog CBX)是PRC1的主要核心蛋白,其家族的成员之一CBX2近年来成为研究的热点。本研究综述了CBX2基因的发现、基因和蛋白质的结构组成及其在人和鼠不同组织的表达情况,阐述了CBX2在哺乳动物性发育中的作用及研究进展,发现CBX2除参与PcG复合体发挥转录抑制作用外,还具有基因转录激活作用,它作为哺乳动物性别决定级联中SRY (Sex region of Y chromosome)的上游基因可直接激活靶基因SF1/NR5A1的表达,如果CBX2基因突变或缺失将使雄性小鼠发生性反转,在人类中造成46,XY性发育障碍(disorders of sex development, DSD),为进一步研究CBX2基因在动物性发育调控中的作用提供依据。
文摘Polycomb chromobox(CBX)proteins regulate gene transcription by maintaining chromatin states,which guide a variety of biological processes.Now,epigenetic regulation of innate immune response is an emerging field.However,the role of CBX proteins in innate immunity remains unclear.We confirmed that the expression of CBX family proteins,especially Cbx2,was decreased in macrophages upon viral infection,and then we investigated the role of Cbx2 in the antiviral immune response.Silencing or knockdown of Cbx2 in macrophages inhibited virus-induced production of IFNp.Furthermore,heterozygous Cbx2 knockout were susceptible to VSV challenge.Mechanistically,Cbx2 binds to and recruits Jmjd3 to the Ifnb promoter,leading to demethylation of H3K27me3 and increased transcription of IFN-β.Together,our study reveals a nontraditional function of a Cbx protein and adds new insight into the epigenetic regulation of antiviral innate immunity.
