TY - JOUR
T1 - A gene-centered C. elegans protein–DNA interaction network provides a framework for functional predictions
AU - Fuxman Bass, Juan I.
AU - Pons, Carles
AU - Kozlowski, Lucie
AU - Reece-Hoyes, John S.
AU - Shrestha, Shaleen
AU - Holdorf, Amy D.
AU - Mori, Akihiro
AU - Myers, Chad L.
AU - Walhout, Albertha J M
N1 - Publisher Copyright:
© 2016 The Authors. Published under the terms of the CC BY 4.0 license
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
KW - C. elegans
KW - gene regulation
KW - protein–DNA interaction network
KW - transcription factors
KW - yeast one-hybrid assays
UR - http://www.scopus.com/inward/record.url?scp=84992650903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992650903&partnerID=8YFLogxK
U2 - 10.15252/msb.20167131
DO - 10.15252/msb.20167131
M3 - Article
C2 - 27777270
AN - SCOPUS:84992650903
SN - 1744-4292
VL - 12
JO - Molecular Systems Biology
JF - Molecular Systems Biology
IS - 10
M1 - 884
ER -