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  coTRaCTE predicts co-occurring transcription factors within cell-type specific enhancers

van Bömmel, A., Love, M. I., Chung, H.-R., & Vingron, M. (2018). coTRaCTE predicts co-occurring transcription factors within cell-type specific enhancers. PLoS Computational Biology, 14(8): e1006372. doi:10.1371/journal.pcbi.1006372.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-66A9-C Version Permalink: http://hdl.handle.net/21.11116/0000-0003-66AA-B
Genre: Journal Article

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 Creators:
van Bömmel, Alena1, Author              
Love, Michael I., Author
Chung, Ho-Ryun2, Author              
Vingron, Martin3, Author              
Affiliations:
1Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              
2Epigenomics (Ho-Ryun Chung), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479658              
3Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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 Abstract: Cell-type specific gene expression is regulated by the combinatorial action of transcription factors (TFs). In this study, we predict transcription factor (TF) combinations that cooperatively bind in a cell-type specific manner. We first divide DNase hypersensitive sites into cell-type specifically open vs. ubiquitously open sites in 64 cell types to describe possible cell-type specific enhancers. Based on the pattern contrast between these two groups of sequences we develop "co-occurring TF predictor on Cell-Type specific Enhancers" (coTRaCTE) - a novel statistical method to determine regulatory TF co-occurrences. Contrasting the co-binding of TF pairs between cell-type specific and ubiquitously open chromatin guarantees the high cell-type specificity of the predictions. coTRaCTE predicts more than 2000 co-occurring TF pairs in 64 cell types. The large majority (70%) of these TF pairs is highly cell-type specific and overlaps in TF pair co-occurrence are highly consistent among related cell types. Furthermore, independently validated co-occurring and directly interacting TFs are significantly enriched in our predictions. Focusing on the regulatory network derived from the predicted co-occurring TF pairs in embryonic stem cells (ESCs) we find that it consists of three subnetworks with distinct functions: maintenance of pluripotency governed by OCT4, SOX2 and NANOG, regulation of early development governed by KLF4, STAT3, ZIC3 and ZNF148 and general functions governed by MYC, TCF3 and YY1. In summary, coTRaCTE predicts highly cell-type specific co-occurring TFs which reveal new insights into transcriptional regulatory mechanisms.

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Language(s): eng - English
 Dates: 2018-07-172018-08-24
 Publication Status: Published online
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 Identifiers: DOI: 10.1371/journal.pcbi.1006372
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Title: PLoS Computational Biology
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 14 (8) Sequence Number: e1006372 Start / End Page: - Identifier: ISSN: 1553-734X
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000017180_1