期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 25, 页码 E4914-E4923出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1704553114
关键词
gene regulation; transcription factor; regulatory element; chromatin regulator; chromatin activity
资金
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB13000000]
- NIH [R01HG007834, P50HG007735]
- National Natural Science Foundation of China [11422108, 61671444, 61621003, 61573207]
The rapid increase of genome-wide datasets on gene expression, chromatin states, and transcription factor (TF) binding locations offers an exciting opportunity to interpret the information encoded in genomes and epigenomes. This task can be challenging as it requires joint modeling of context-specific activation of cis-regulatory elements (REs) and the effects on transcription of associated regulatory factors. To meet this challenge, we propose a statistical approach based on paired expression and chromatin accessibility (PECA) data across diverse cellular contexts. In our approach, we model (i) the localization to REs of chromatin regulators (CRs) based on their interaction with sequence-specific TFs, (ii) the activation of REs due to CRs that are localized to them, and (iii) the effect of TFs bound to activated REs on the transcription of target genes (TGs). The transcriptional regulatory network inferred by PECA provides a detailed view of how trans-and cis-regulatory elements work together to affect gene expression in a context-specific manner. We illustrate the feasibility of this approach by analyzing paired expression and accessibility data from the mouse Encyclopedia of DNA Elements (ENCODE) and explore various applications of the resulting model.
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