Genome-wide identification of binding sites defines distinct functions for Caenorhabditis elegans PHA-4/FOXA in development and environmental response.
Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles.
Zhong
Mei
M
Department of Molecular Cellular Developmental Biology, Yale University, New Haven, Connecticut, United States of America.
Niu
Wei
W
Lu
Zhi John
ZJ
Sarov
Mihail
M
Murray
John I
JI
Janette
Judith
J
Raha
Debasish
D
Sheaffer
Karyn L
KL
Lam
Hugo Y K
HY
Preston
Elicia
E
Slightham
Cindie
C
Hillier
LaDeana W
LW
Brock
Trisha
T
Agarwal
Ashish
A
Auerbach
Raymond
R
Hyman
Anthony A
AA
Gerstein
Mark
M
Mango
Susan E
SE
Kim
Stuart K
SK
Waterston
Robert H
RH
Reinke
Valerie
V
Snyder
Michael
M
D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004777:Environment; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000235:genetics; D049751:Genome, Helminth / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013217:Starvation; D016019:Survival Analysis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C113277:Pha-4 protein, C elegans; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D012319:RNA Polymerase II