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De novo recruitment of Polycomb-group proteins in Drosophila embryos

机译:De Novo招募Drosophila胚胎中的Polycomb-Group蛋白

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摘要

Polycomb-group (PcG)-mediated transcriptional repression of target genes can be delineated into two phases. First, following initial repression of target genes by gene-specific transcription factors, PcG proteins recognize the repressed state and assume control of the genes' repression. Second, once the silenced state is established, PcG proteins may maintain repression through an indefinite number of cell cycles. Little is understood about how PcG proteins initially recognize the repressed state of target genes and the steps leading to de novo establishment of PcG-mediated repression. We describe a genetic system in which a Drosophila PcG target gene, giant (gt), is ubiquitously repressed during early embryogenesis by a maternally expressed transcription factor, and show the temporal recruitment of components of three PcG protein complexes: PhoRC, PRC1 and PRC2. We show that de novo PcG recruitment follows a temporal hierarchy in which PhoRC stably localizes at the target gene at least 1 h before stable recruitment of PRC2 and concurrent trimethylation of histone H3 at lysine 27 (H3K27me3). The presence of PRC2 and increased levels of H3K27me3 are found to precede stable binding by PRC1.
机译:polycomb-group(pcg)介导的靶基因的转录抑制可以描绘成两个阶段。首先,在通过基因特异性转录因子初始抑制靶基因之后,PCG蛋白识别抑制状态并防范基因的抑制。其次,一旦建立了沉默状态,PCG蛋白质可以通过无限数量的细胞循环维持抑制。关于PCG蛋白最初识别靶基因的压抑状态以及导致De Novo建立PCG介导的抑制的步骤的难题一点。我们描述了一种遗传系统,其中果蝇PCG靶基因巨大(GT)在早期胚胎发生过程中通过母体表达转录因子普遍存在,并且显示了三种PCG蛋白复合物组分的时间募集:Phorc,PRC1和PRC2。我们表明De Novo PCG募集遵循颞级层次结构,其中Phorc在稳定募集PRC2之前至少1小时稳定地定位在赖氨酸27(H3K27ME3)的组蛋白H3的同时三甲基化。发现PRC2的存在和增加的H3K27ME3水平,以便于PRC1之前稳定结合。

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