Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
University of Minnesota Informatics Institute, Minneapolis, MN 55455, USA.
Genetics. 2021 Oct 2;219(2). doi: 10.1093/genetics/iyab107.
Embryonic patterning is critically dependent on zygotic genome activation (ZGA). In Drosophila melanogaster embryos, the pioneer factor Zelda directs ZGA, possibly in conjunction with other factors. Here, we have explored the novel involvement of Chromatin-Linked Adapter for MSL Proteins (CLAMP) during ZGA. CLAMP binds thousands of sites genome-wide throughout early embryogenesis. Interestingly, CLAMP relocates to target promoter sequences across the genome when ZGA is initiated. Although there is a considerable overlap between CLAMP and Zelda binding sites, the proteins display distinct temporal dynamics. To assess whether CLAMP occupancy affects gene expression, we analyzed transcriptomes of embryos zygotically compromised for either clamp or zelda and found that transcript levels of many zygotically activated genes are similarly affected. Importantly, compromising either clamp or zelda disrupted the expression of critical segmentation and sex determination genes bound by CLAMP (and Zelda). Furthermore, clamp knockdown embryos recapitulate other phenotypes observed in Zelda-depleted embryos, including nuclear division defects, centrosome aberrations, and a disorganized actomyosin network. Based on these data, we propose that CLAMP acts in concert with Zelda to regulate early zygotic transcription.
胚胎模式形成严重依赖于合子基因组激活(ZGA)。在黑腹果蝇胚胎中,先驱因子 Zelda 指导 ZGA,可能与其他因子一起。在这里,我们探索了染色质连接的 MSL 蛋白(CLAMP)在 ZGA 过程中的新作用。CLAMP 在整个早期胚胎发生过程中在全基因组范围内结合数千个位点。有趣的是,当 ZGA 启动时,CLAMP 会重新定位到基因组上的目标启动子序列。虽然 CLAMP 和 Zelda 结合位点之间有相当大的重叠,但这些蛋白质显示出不同的时间动态。为了评估 CLAMP 占据是否影响基因表达,我们分析了 zygotically 受到 clamp 或 zelda 影响的胚胎的转录组,发现许多 zygotically 激活的基因的转录水平受到类似的影响。重要的是,剥夺 clamp 或 zelda 都会破坏 CLAMP(和 Zelda)结合的关键分割和性别决定基因的表达。此外,clamp 敲低胚胎再现了在 Zelda 耗尽胚胎中观察到的其他表型,包括核分裂缺陷、中心体异常和肌动球蛋白网络紊乱。基于这些数据,我们提出 CLAMP 与 Zelda 协同作用来调节早期合子转录。