E2F coregulates an essential HSF developmental program that is distinct from the heat-shock response.
Heat-shock factor (HSF) is the master transcriptional regulator of the heat-shock response (HSR) and is essential for stress resilience. HSF is also required for metazoan development; however, its function and regulation in this process are poorly understood. Here, we characterize the genomic distribution and transcriptional activity of Caenorhabditis elegans HSF-1 during larval development and show that the developmental HSF-1 transcriptional program is distinct from the HSR. HSF-1 developmental activation requires binding of E2F/DP to a GC-rich motif that facilitates HSF-1 binding to a heat-shock element (HSE) that is degenerate from the consensus HSE sequence and adjacent to the E2F-binding site at promoters. In contrast, induction of the HSR is independent of these promoter elements or E2F/DP and instead requires a distinct set of tandem canonical HSEs. Together, E2F and HSF-1 directly regulate a gene network, including a specific subset of chaperones, to promote protein biogenesis and anabolic metabolism, which are essential in development.
Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA.
Jian
J
Li
Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA.
Laetitia
L
Chauve
Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA.
Grace
G
Phelps
Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA.
Renée M
RM
Brielmann
Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA.
Richard I
RI
Morimoto
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism*; D053263:Gene Regulatory Networks / Q000235:genetics; D049751:Genome, Helminth / Q000235:genetics; D018869:Heat-Shock Response / Q000235:genetics*; D007814:Larva / Q000235:genetics / Q000254:growth & development; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding
D029742:Caenorhabditis elegans Proteins; D050684:E2F Transcription Factors
Caenorhabditis elegans; E2F transcription factor; development; heat-shock factor (HSF); molecular chaperones; stress response; transcription regulation
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