DOI: 10.1101/gad.453808. Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor

Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor

10.1101/gad.453808

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

The circadian clock enables the anticipation of daily recurring environmental changes by presetting an organism’s physiology and behavior. Driven and synchronized by a central pacemaker in the brain, circadian output genes fine-tune a wide variety of physiological parameters in peripheral organs. However, only a subset of circadianly transcribed genes seems to be directly regulated by core clock proteins. Assuming that yet unidentified transcription factors may exist in the circadian transcriptional network, we set out to develop a novel technique, differential display of DNA-binding proteins (DDDP), which we used to screen mouse liver nuclear extracts. In addition to several established circadian transcription factors, we found DNA binding of heat-shock factor 1 (HSF1) to be highly rhythmic. HSF1 drives the expression of heat-shock proteins at the onset of the dark phase, when the animals start to be behaviorally active. Furthermore, Hsf1-deficient mice have a longer free-running period than wild-type littermates, suggesting a combined role for HSF1 in the mammalian timekeeping and cytoprotection systems. Our results also suggest that the new screening method DDDP is not limited to the identification of circadian transcription factors but can be applied to discover novel transcriptional regulators in various biological systems.

Bibliography

Reinke, H., Saini, C., Fleury-Olela, F., Dibner, C., Benjamin, I. J., & Schibler, U. (2008). Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor. Genes & Development, 22(3), 331â345.

Authors 6

Hans Reinke (first)
Camille Saini (additional)
Fabienne Fleury-Olela (additional)
Charna Dibner (additional)
Ivor J. Benjamin (additional)
Ueli Schibler (additional)

References 70 Referenced 209

10.1101/gad.1044503
10.1016/S0960-9822(02)00759-5
10.1007/978-0-387-39975-1_8
10.1016/S0092-8674(00)81199-X
10.1126/science.289.5488.2344
10.1186/1471-2148-4-42
10.1038/76469
10.1016/S0960-9822(02)01145-4
10.1042/bj3170329
10.1126/science.1124646
10.1042/BJ20021176
10.1101/gr.849004
10.1101/gad.183500
10.1177/0748730406294767
10.1016/S0960-9822(02)00765-0
10.1016/j.febslet.2006.05.023
10.1042/BJ20020269
{'key': '2021111608001638000_22.3.331.18', 'first-page': '797', 'article-title': 'DNA-binding specificity of PAR and C/EBP leucine zipper proteins: A single amino acid substitution in the C/EBP DNA-binding domain confers PAR-like specificity to C/EBP', 'volume': '377', 'author': 'Falvey,', 'year': '1996', 'journal-title': 'Biol. Chem.'} / Biol. Chem. / DNA-binding specificity of PAR and C/EBP leucine zipper proteins: A single amino acid substitution in the C/EBP DNA-binding domain confers PAR-like specificity to C/EBP by Falvey, (1996)
10.1016/j.cub.2006.08.053
10.1002/j.1460-2075.1996.tb00365.x / EMBO J. / The two PAR leucine zipper proteins, TEF and DBP, display similar circadian and tissue-specific expression, but have different target promoter preferences by Fonjallaz, (1996)
10.1210/me.8.9.1253
10.1074/jbc.M506288200
10.1101/gad.301404
10.1016/j.cmet.2006.04.015
10.1038/nrm2106
10.1016/j.conb.2006.09.001
10.1038/343536a0
10.1074/jbc.M001677200
10.1101/gr.6.10.986
10.1093/emboj/20.14.3800
10.1523/JNEUROSCI.0006-07.2007
10.1016/j.febslet.2004.06.087
10.1093/nar/29.11.e51
10.1371/journal.pbio.0050034
10.1101/gad.7.10.1871
10.1016/S0092-8674(01)00610-9
10.1016/j.cell.2007.02.047
10.1093/emboj/16.22.6762
10.1038/35007527 / Nature / Towards a molecular understanding of adaptive thermogenesis by Lowell, (2000)
10.1038/352497a0
10.1145/272991.272995
10.1152/physiolgenomics.00066.2007
10.1073/pnas.0611724104
10.1016/j.mce.2006.03.007
10.1016/j.cell.2004.11.015
10.1016/S0092-8674(02)00722-5
10.1016/S0962-8924(03)00006-0
10.1016/S0092-8674(02)00825-5
10.1016/j.cub.2006.04.026
10.1002/(SICI)1097-010X(19960501)275:1<67::AID-JEZ10>3.0.CO;2-U
10.1038/nature00965
10.1038/ng1738
10.1101/gad.14.6.679 / Genes & Dev. / CLOCK, an essential pacemaker component, controls expression of the circadian transcription factor DBP by Ripperger, (2000)
10.1074/jbc.M611801200
Sambrook, J. Russel, D. (2000) Molecular cloning: A laboratory manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY).
10.1016/j.tins.2004.12.009
10.1101/gr.171601
10.1038/nature744
10.1016/S0378-1119(99)00357-1
10.1038/nature00906
10.1126/science.270.5235.484
10.1007/3-540-29717-0_2 / Handb. Exp. Pharmacol. / Feedback regulation of the heat shock response by Voellmy, (2006)
10.1016/j.cub.2004.11.057
10.1093/nar/24.1.238
10.1016/0092-8674(90)90421-A
{'key': '2021111608001638000_22.3.331.66', 'first-page': '7219', 'article-title': 'Physical isolation of nascent RNA chains transcribed by RNA polymerase II: Evidence for cotranscriptional splicing', 'volume': '14', 'author': 'Wuarin,', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Physical isolation of nascent RNA chains transcribed by RNA polymerase II: Evidence for cotranscriptional splicing by Wuarin, (1994)
10.1093/emboj/18.21.5943
10.1126/science.288.5466.682
10.1093/emboj/cdf528
10.1073/pnas.0409763102

Dates

Type	When
Created	17 years, 7 months ago (Feb. 1, 2008, 1:44 p.m.)
Deposited	3 years, 9 months ago (Nov. 16, 2021, 12:13 p.m.)
Indexed	3 days, 13 hours ago (Aug. 30, 2025, 12:43 p.m.)
Issued	17 years, 7 months ago (Feb. 1, 2008)
Published	17 years, 7 months ago (Feb. 1, 2008)
Published Online	17 years, 7 months ago (Feb. 1, 2008)
Published Print	17 years, 7 months ago (Feb. 1, 2008)

Funders 0

None

BibTeX

@article{Reinke_2008, title={Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor}, volume={22}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.453808}, DOI={10.1101/gad.453808}, number={3}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Reinke, Hans and Saini, Camille and Fleury-Olela, Fabienne and Dibner, Charna and Benjamin, Ivor J. and Schibler, Ueli}, year={2008}, month=feb, pages={331–345} }

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