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H3K27me3 Signal in the Cis Regulatory Elements Reveals the Differentiation Potential of Progenitors

本站小编 Free考研考试/2022-01-03

Drosophila neural development undergoes extensive chromatin remodeling and precise epigenetic regulation. However, the roles of chromatin remodeling in establishment and maintenance of cell identity during cell fate transition remain enigmatic. Here, we compared the changes in gene expression, as well as the dynamics of nucleosome positioning and key histone modifications between the four major neural cell types during Drosophila neural development. We find that the neural progenitors can be separated from the terminally differentiated cells based on their gene expression profiles, whereas nucleosome distribution in the flanking regions of transcription start sites fails to identify the relationships between the progenitors and the differentiated cells. H3K27me3 signal in promoters and enhancers can not only distinguish the progenitors from the differentiated cells but also identify the differentiation path of the neural stem cells (NSCs) to the intermediate progenitor cells to the glial cells. In contrast, H3K9ac signal fails to identify the differentiation path, although it activates distinct sets of genes with neuron-specific and glia-related functions during the differentiation of the NSCs into neurons and glia, respectively. Together, our study provides novel insights into the crucial roles of chromatin remodeling in determining cell type during Drosophila neural development.
果蝇神经发育中发生广泛的染色质重塑和精确的表观调控。然而,染色质重塑在细胞命运转化中细胞身份的建立与维持中的作用并不清楚。这里,我们比较了果蝇神经发育中四种主要神经细胞之间的基因表达变化、核小体定位与关键组蛋白修饰的动态变化。结果发现基因表达谱能分开神经前体细胞与终端分化神经细胞,但转录起始位点附近的核小体占有不能区分二者。启动子与增强子上的H3K27me3信号不但能区分神经前体细胞与分化的神经细胞,而且可以鉴定出神经前体细胞到中间神经前体细胞再到神经胶质细胞的分化路径。相对比,H3K9ac信号不能鉴定出这条分化路径,不过它可以在神经前体细胞分化为神经元与神经胶质细胞过程中,分别激活具有神经元特异与神经胶质特异功能的不同基因集。总之,我们的研究对果蝇神经发育过程中染色质重塑功能提出新见解。





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http://gpb.big.ac.cn/articles/download/711
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