期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 51, 页码 21521-21526出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0904863106
关键词
ChIP binding; pluripotency; RNA-Seq; transcription regulation
资金
- National Institutes of Health [R01HG004634, R01HG003903]
- National Science Foundation [DMS-0805491]
- California Institute for Regenerative Medicine (CIRM) [RC1-00133]
- Division Of Mathematical Sciences
- Direct For Mathematical & Physical Scien [0805491] Funding Source: National Science Foundation
Next-generation sequencing has greatly increased the scope and the resolution of transcriptional regulation study. RNA sequencing (RNA-Seq) and ChIP-Seq experiments are now generating comprehensive data on transcript abundance and on regulator-DNA interactions. We propose an approach for an integrated analysis of these data based on feature extraction of ChIP-Seq signals, principal component analysis, and regression-based component selection. Compared with traditional methods, our approach not only offers higher power in predicting gene expression from ChIP-Seq data but also provides a way to capture cooperation among regulators. In mouse embryonic stem cells (ESCs), we find that a remarkably high proportion of variation in gene expression (65%) can be explained by the binding signals of 12 transcription factors (TFs). Two groups of TFs are identified. Whereas the first group (E2f1, Myc, Mycn, and Zfx) act as activators in general, the second group (Oct4, Nanog, Sox2, Smad1, Stat3, Tcfcp2l1, and Esrrb) may serve as either activator or repressor depending on the target. The two groups of TFs cooperate tightly to activate genes that are differentially up-regulated in ESCs. In the absence of binding by the first group, the binding of the second group is associated with genes that are repressed in ESCs and derepressed upon early differentiation.
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