A systematic method to identify modulation of transcriptional regulation via chromatin activity reveals regulatory network during mESC differentiation

doi:10.1038/srep22656

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	A systematic method to identify modulation of transcriptional regulation via chromatin activity reveals regulatory network during mESC differentiation
	Duren, Zhana; Wang, Yong
	2016-03-07
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	6 页码:12
摘要	Chromatin regulators (CRs) are crucial for connecting the chromatin level and transcriptome level by modulating chromatin structures, establishing, and maintaining epigenetic modifications. We present a systematic method to identify MOdulation of transcriptional regulation via CHromatin Activity (MOCHA) from gene expression data and demonstrate its advantage in associating CRs to their chromatin localization and understand CRs' function. We first re-construct the CRs modulation network by integrating the correlation and conditional correlation concepts. Then we quantify the chromatin activity as hidden variable in network by integrating the upstream and downstream information. We applied MOCHA to systematically explore the interplay of CRs, TFs, and target genes in mouse embryonic stem cells (ESC). As a result, MOCHA identified 420 chromatin regulators with modulation preference, including Pou5f1 and Eed. We found that BAF complex, NuRD complex, and polycomb-group proteins, regulate the delicate balance between pluripotency and differentiation by modulating key TFs including Klf4, Tcf3, and Max; NuRD complex members Mbd3 and Hdac1 may modulate Klf4 to achieve its dual functional roles in pluripotent and differentiation stages; Imprinted gene H19 and Igf2 are modulated by DNA methylation, histone acetylation, and insulator CTCF. Finally, we analyzed CR's combinational modulation pattern by constructing a CR-CR interaction network.
DOI	10.1038/srep22656
语种	英语
资助项目	Strategic Priority Research Program of the Chinese Academy of Sciences[XDB13040700] ; National Natural Science Foundation of China (NSFC)[61171007] ; National Natural Science Foundation of China (NSFC)[11131009] ; National Natural Science Foundation of China (NSFC)[11422108]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000373282500001
出版者	NATURE PUBLISHING GROUP
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/22396
专题	应用数学研究所
通讯作者	Wang, Yong
作者单位	Chinese Acad Sci, Acad Math & Syst Sci, Natl Ctr Math & Interdisciplinary Sci, Beijing 100190, Peoples R China
推荐引用方式 GB/T 7714	Duren, Zhana,Wang, Yong. A systematic method to identify modulation of transcriptional regulation via chromatin activity reveals regulatory network during mESC differentiation[J]. SCIENTIFIC REPORTS,2016,6:12.
APA	Duren, Zhana,&Wang, Yong.(2016).A systematic method to identify modulation of transcriptional regulation via chromatin activity reveals regulatory network during mESC differentiation.SCIENTIFIC REPORTS,6,12.
MLA	Duren, Zhana,et al."A systematic method to identify modulation of transcriptional regulation via chromatin activity reveals regulatory network during mESC differentiation".SCIENTIFIC REPORTS 6(2016):12.