TY - JOUR
T1 - E2F coregulates an essential HSF developmental program that is distinct from the heat-shock response
AU - Li, Jian
AU - Chauve, Laetitia
AU - Phelps, Grace
AU - Brielmann, Renée M.
AU - Morimoto, Richard I.
N1 - Funding Information:
We thank Erik Andersen for helpful discussions on the DRM complex, H. Robert Horvitz and David Fay for sharing strains, Jean-Louis Bessereau for generous advice and technical support on generating the Mos1 transposase-mediated single-copy gene insertion (MosSCI) transgenic line, Janay Terry for assisting with the NLS::GFP line, Yoko Shibata for confocal microscopy, and members of the Morimoto laboratory for their scientific advice and comments on the manuscript. We also thank the Biopolymers Facility at Harvard Medical School and the High- Throughput Genome Analysis Core at the Institute for Genomics and Systems Biology at the University of Chicago for sequencing support. J.L. was supported by post-doctoral awards from the National Ataxia Foundation, the BrightFocus Foundation for Alzheimer?s Disease Research, and the Chicago Biomedical Consortium. R.I.M. was supported by grants from the National Institutes of Health (National Institute on Aging and National Institute of Mental Health), the Ellison Medical Foundation, the Glenn Foundation, the Chicago Biomedical Consortium, and the Daniel F. and Ada L. Rice Foundation.
PY - 2016/9/15
Y1 - 2016/9/15
N2 - 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.
AB - 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.
KW - Caenorhabditis elegans
KW - Development
KW - E2F transcription factor
KW - Heat-shock factor (HSF)
KW - Molecular chaperones
KW - Stress response
KW - Transcription regulation
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U2 - 10.1101/gad.283317.116
DO - 10.1101/gad.283317.116
M3 - Article
C2 - 27688402
AN - SCOPUS:84990986075
VL - 30
SP - 2062
EP - 2075
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 18
ER -