A gene-centered C. elegans protein–DNA interaction network provides a framework for functional predictions

Juan I. Fuxman Bass; Carles Pons; Lucie Kozlowski; John S. Reece-Hoyes; Shaleen Shrestha; Amy D. Holdorf; Akihiro Mori; Chad L. Myers; Albertha J M Walhout

doi:10.15252/msb.20167131

A gene-centered C. elegans protein–DNA interaction network provides a framework for functional predictions

Juan I. Fuxman Bass, Carles Pons, Lucie Kozlowski, John S. Reece-Hoyes, Shaleen Shrestha, Amy D. Holdorf, Akihiro Mori, Chad L. Myers, Albertha J M Walhout

Computer Science and Engineering

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein–DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences. Here, we delineated the largest gene-centered metazoan PDI network to date by examining interactions between 90% of C. elegans TFs and 15% of gene promoters. We used this network as a backbone to predict TF binding sites for 77 TFs, two-thirds of which are novel, as well as integrate gene expression, protein–protein interaction, and phenotypic data to predict regulatory and biological functions for multiple genes and TFs.

Original language	English (US)
Article number	884
Journal	Molecular Systems Biology
Volume	12
Issue number	10
DOIs	https://doi.org/10.15252/msb.20167131
State	Published - Oct 1 2016

Bibliographical note

Funding Information:
We thank members of the Walhout Lab for discussions and critical reading of the manuscript. We thank Alos Diallo for assistance in image processing analyses. Strains were provided by the C. elegans Genetics Center (CGC), which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440); and by the National BioResource Project, Japan. This work was supported by US National Institutes of Health grant GM082971 to AJMW and CLM.

Publisher Copyright:
© 2016 The Authors. Published under the terms of the CC BY 4.0 license

Keywords

C. elegans
gene regulation
protein–DNA interaction network
transcription factors
yeast one-hybrid assays

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10.15252/msb.20167131

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title = "A gene-centered C. elegans protein–DNA interaction network provides a framework for functional predictions",

abstract = "Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein–DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences. Here, we delineated the largest gene-centered metazoan PDI network to date by examining interactions between 90% of C. elegans TFs and 15% of gene promoters. We used this network as a backbone to predict TF binding sites for 77 TFs, two-thirds of which are novel, as well as integrate gene expression, protein–protein interaction, and phenotypic data to predict regulatory and biological functions for multiple genes and TFs.",

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note = "Funding Information: We thank members of the Walhout Lab for discussions and critical reading of the manuscript. We thank Alos Diallo for assistance in image processing analyses. Strains were provided by the C. elegans Genetics Center (CGC), which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440); and by the National BioResource Project, Japan. This work was supported by US National Institutes of Health grant GM082971 to AJMW and CLM. Publisher Copyright: {\textcopyright} 2016 The Authors. Published under the terms of the CC BY 4.0 license",

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