Diverse transcription factor binding features revealed by genome-wide ChIP-seq in C. elegans
- Wei Niu1,
- Zhi John Lu2,3,
- Mei Zhong4,
- Mihail Sarov5,
- John I. Murray6,
- Cathleen M. Brdlik7,
- Judith Janette1,
- Chao Chen2,3,
- Pedro Alves3,
- Elicia Preston6,
- Cindie Slightham8,
- Lixia Jiang7,
- Anthony A. Hyman5,
- Stuart K. Kim8,
- Robert H. Waterston6,
- Mark Gerstein2,3,
- Michael Snyder7,9 and
- Valerie Reinke1,9
- 1 Department of Genetics, Yale University, New Haven, Connecticut 06520, USA;
- 2 Department of Molecular Biochemistry and Biophysics, Yale University, New Haven, Connecticut 06520, USA;
- 3 Program in Computation Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA;
- 4 Stem Cell Center, Yale University, New Haven, Connecticut 06520, USA;
- 5 Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany;
- 6 Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA;
- 7 Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;
- 8 Department of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305, USA
Abstract
Regulation of gene expression by sequence-specific transcription factors is central to developmental programs and depends on the binding of transcription factors with target sites in the genome. To date, most such analyses in Caenorhabditis elegans have focused on the interactions between a single transcription factor with one or a few select target genes. As part of the modENCODE Consortium, we have used chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) to determine the genome-wide binding sites of 22 transcription factors (ALR-1, BLMP-1, CEH-14, CEH-30, EGL-27, EGL-5, ELT-3, EOR-1, GEI-11, HLH-1, LIN-11, LIN-13, LIN-15B, LIN-39, MAB-5, MDL-1, MEP-1, PES-1, PHA-4, PQM-1, SKN-1, and UNC-130) at diverse developmental stages. For each factor we determined candidate gene targets, both coding and non-coding. The typical binding sites of almost all factors are within a few hundred nucleotides of the transcript start site. Most factors target a mixture of coding and non-coding target genes, although one factor preferentially binds to non-coding RNA genes. We built a regulatory network among the 22 factors to determine their functional relationships to each other and found that some factors appear to act preferentially as regulators and others as target genes. Examination of the binding targets of three related HOX factors—LIN-39, MAB-5, and EGL-5—indicates that these factors regulate genes involved in cellular migration, neuronal function, and vulval differentiation, consistent with their known roles in these developmental processes. Ultimately, the comprehensive mapping of transcription factor binding sites will identify features of transcriptional networks that regulate C. elegans developmental processes.
Footnotes
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↵9 Corresponding authors.
E-mail valerie.reinke{at}yale.edu; fax (203) 785-6333.
E-mail mpsnyder{at}stanford.edu.
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[Supplemental material is available for this article. The ChIP-seq data from this study have been submitted to the NCBI Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) under accession nos. GSE14545, GSE15625, GSE17454, GSE17456, GSE25779, GSE25782–GSE25785, GSE25787, GSE25795–GSE25796, GSE25798–GSE25805, GSE25808–GSE25811, and GSE26152–GSE26153.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.114587.110.
- Received August 25, 2010.
- Accepted December 8, 2010.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
