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Dynamic changes in the genomic localization of DNA replication-related element binding factor during the cell cycle

机译:细胞周期中DNA复制相关元件结合因子的基因组定位的动态变化

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DREF was first characterized for its role in the regulation of transcription of genes encoding proteins involved in DNA replication and found to interact with sequences similar to the DNA recognition motif of the BEAF-32 insulator protein. Insulators are DNA-protein complexes that mediate intra- and inter-chromosome interactions. Several DNA-binding insulator proteins have been described in Drosophila, including BEAF-32, dCTCF and Su(Hw). Here we find that DREF and BEAF-32 co-localize at the same genomic sites, but their enrichment shows an inverse correlation. Furthermore, DREF co-localizes in the genome with other insulator proteins, suggesting that the function of this protein may require components of Drosophila insulators. This is supported by the finding that mutations in insulator proteins modulate DREF-induced cell proliferation. DREF persists bound to chromatin during mitosis at a subset of sites where it also co-localizes with dCTCF, BEAF-32 and CP190. These sites are highly enriched for sites where Orc2 and Mcm2 are present during interphase and at the borders of topological domains of chromosomes defined by Hi-C. The results suggest that DREF and insulator proteins may help maintain chromosome organization during the cell cycle and mark a subset of genomic sites for the assembly of pre-replication complexes and gene bookmarking during the M/G1 transition.
机译:DREF最初因其在调控参与DNA复制的蛋白质的基因转录调控中的作用而被表征,并发现其与类似于BEAF-32绝缘子蛋白质的DNA识别基序的序列相互作用。绝缘子是介导染色体内和染色体间相互作用的DNA-蛋白质复合物。果蝇中已经描述了几种结合DNA的绝缘子蛋白,包括BEAF-32,dCTCF和Su(Hw)。在这里,我们发现DREF和BEAF-32共定位在相同的基因组位点,但是它们的富集显示出反相关。此外,DREF与其他绝缘子蛋白在基因组中共定位,表明该蛋白的功能可能需要果蝇绝缘子的成分。绝缘蛋白突变调节DREF诱导的细胞增殖的发现支持了这一点。在有丝分裂期间,DREF仍然与染色质结合,并与dCTCF,BEAF-32和CP190共同定位在一个子集。这些位点高度富集了在相间过程中以及在由Hi-C定义的染色体拓扑结构域边界处存在Orc2和Mcm2的位点。结果表明,DREF和绝缘蛋白可以帮助维持细胞周期中的染色体组织,并标记基因组位点的子集,以在M / G1过渡过程中组装复制前复合体和标记基因。

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