CpG island-mediated global gene regulatory modes in mouse embryonic stem cells
CpG island-mediated global gene regulatory modes in mouse embryonic stem cells
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DOI：
10.1038/ncomms6490
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发表时间：
2014-11-01
影响因子：
16.6
通讯作者：
Kim, Jonghwan
中科院分区：
文献类型：
--
作者：
Beck, Samuel;Lee, Bum-Kyu;Kim, Jonghwan
转录调控和表观遗传调控是真核生物基因表达调控的基础。在这里，我们进行了4200大测序数据集的纲要分析，以阐明全球基因表达程序在小鼠胚胎干细胞（ES）的调控逻辑。我们定义了四个主要类别的DNA结合蛋白（核心，PRC，MYC和CTCF）的基础上，他们的目标共同占有，并发现之间的相互调节MYC和PRC类的活性几乎所有的基因的控制下的CpG岛（CGI）的启动子。这种CGI依赖的调控模式解释了早期发育过程中CGI基因和CGI基因之间的功能分离。通过定义基于核心类的共占据的活性增强子，我们进一步证明了它们在含CGI的基因表达中的加性作用和在无CGI的基因表达中的细胞类型特异性作用。总之，我们的分析提供了新的见解，以前未知的CGI依赖的全球基因调控模式。
Both transcriptional and epigenetic regulations are fundamental for the control of eukaryotic gene expression. Here we perform a compendium analysis of 4200 large sequencing data sets to elucidate the regulatory logic of global gene expression programs in mouse embryonic stem (ES) cells. We define four major classes of DNA-binding proteins (Core, PRC, MYC and CTCF) based on their target co-occupancy, and discover reciprocal regulation between the MYC and PRC classes for the activity of nearly all genes under the control of the CpG island (CGI)-containing promoters. This CGI-dependent regulatory mode explains the functional segregation between CGI-containing and CGI-less genes during early development. By defining active enhancers based on the co-occupancy of the Core class, we further demonstrate their additive roles in CGI-containing gene expression and cell type-specific roles in CGI-less gene expression. Altogether, our analyses provide novel insights into previously unknown CGI-dependent global gene regulatory modes.