Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo.
Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo.
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DOI：
10.1101/gr.192682.115
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发表时间：
2015-11
期刊：
影响因子：
7
通讯作者：
Harrison MM
中科院分区：
文献类型：
--
作者：
Schulz KN;Bondra ER;Moshe A;Villalta JE;Lieb JD;Kaplan T;McKay DJ;Harrison MM
从特定的生殖细胞到多能细胞群体的转变在受精后迅速发生。在这一发育转变过程中，合子基因组在很大程度上是转录静止的，并经历了显着的染色质重塑。在果蝇中，DNA结合蛋白Zelda（也称为Vielfaltig）是这种转变和合子基因组转录激活所必需的。开放染色质与塞尔达结合位点相关，更普遍的是与活跃转录区域相关。尽管如此，塞尔达影响整个基因组染色质可及性的程度在很大程度上是未知的。在这里，我们使用甲醛辅助分离的调控元件，以确定塞尔达在早期胚胎开放染色质的调节区域的作用。我们证明塞尔达是必不可少的数百个区域的开放染色质。这种塞尔达介导的染色质可及性有助于转录因子的募集和早期基因表达。因此，塞尔达拥有先锋因素的一些关键特征。出乎意料的是，即使在没有塞尔达的情况下，塞尔达结合区域的大子集的染色质仍然是开放的。GAGA因子结合基序和胚胎GAGA因子结合在这些区域特异性富集。我们认为，塞尔达和GAGA因子的功能，以指定开放染色质的网站，并共同促进早期胚胎基因组的重塑。
The transition from a specified germ cell to a population of pluripotent cells occurs rapidly following fertilization. During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling. In Drosophila, the DNA-binding protein Zelda (also known as Vielfaltig) is required for this transition and for transcriptional activation of the zygotic genome. Open chromatin is associated with Zelda-bound loci, as well as more generally with regions of active transcription. Nonetheless, the extent to which Zelda influences chromatin accessibility across the genome is largely unknown. Here we used formaldehyde-assisted isolation of regulatory elements to determine the role of Zelda in regulating regions of open chromatin in the early embryo. We demonstrate that Zelda is essential for hundreds of regions of open chromatin. This Zelda-mediated chromatin accessibility facilitates transcription-factor recruitment and early gene expression. Thus, Zelda possesses some key characteristics of a pioneer factor. Unexpectedly, chromatin at a large subset of Zelda-bound regions remains open even in the absence of Zelda. The GAGA factor-binding motif and embryonic GAGA factor binding are specifically enriched in these regions. We propose that both Zelda and GAGA factor function to specify sites of open chromatin and together facilitate the remodeling of the early embryonic genome.