Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice

Kazuhiro Shimomura; Vivek Kumar; Nobuya Koike; Tae Kyung Kim; Jason Chong; Ethan D. Buhr; Andrew R. Whiteley; Sharon S. Low; Chiaki Omura; Deborah Fenner; Joseph R. Owens; Marc Richards; Seung Hee Yoo; Hee Kyung Hong; Martha H. Vitaterna; Joseph Bass; Mathew T. Pletcher; Tim Wiltshire; John Hogenesch; Phillip L. Lowrey; Joseph S. Takahashi

doi:10.7554/eLife.00426

Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice

Kazuhiro Shimomura, Vivek Kumar, Nobuya Koike, Tae Kyung Kim, Jason Chong, Ethan D. Buhr, Andrew R. Whiteley, Sharon S. Low, Chiaki Omura, Deborah Fenner, Joseph R. Owens, Marc Richards, Seung Hee Yoo, Hee Kyung Hong, Martha H. Vitaterna, Joseph Bass, Mathew T. Pletcher, Tim Wiltshire, John Hogenesch, Phillip L. LowreyJoseph S. Takahashi

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55 Scopus citations

Abstract

Genetic and molecular approaches have been critical for elucidating the mechanism of the mammalian circadian clock. Here, we demonstrate that the ClockΔ19 mutant behavioral phenotype is significantly modified by mouse strain genetic background. We map a suppressor of the ClockΔ19 mutation to a ~900 kb interval on mouse chromosome 1 and identify the transcription factor, Usf1, as the responsible gene. A SNP in the promoter of Usf1 causes elevation of its transcript and protein in strains that suppress the Clock mutant phenotype. USF1 competes with the CLOCK:BMAL1 complex for binding to E-box sites in target genes. Saturation binding experiments demonstrate reduced affinity of the CLOCKΔ19:BMAL1 complex for E-box sites, thereby permitting increased USF1 occupancy on a genome-wide basis. We propose that USF1 is an important modulator of molecular and behavioral circadian rhythms in mammals.

Original language	English (US)
Article number	e00426
Journal	eLife
Volume	2013
Issue number	2
DOIs	https://doi.org/10.7554/eLife.00426
State	Published - Apr 9 2013

Funding

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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10.7554/eLife.00426

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Shimomura, K., Kumar, V., Koike, N., Kim, T. K., Chong, J., Buhr, E. D., Whiteley, A. R., Low, S. S., Omura, C., Fenner, D., Owens, J. R., Richards, M., Yoo, S. H., Hong, H. K., Vitaterna, M. H., Bass, J., Pletcher, M. T., Wiltshire, T., Hogenesch, J., ... Takahashi, J. S. (2013). Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice. eLife, 2013(2), Article e00426. https://doi.org/10.7554/eLife.00426

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title = "Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice",

abstract = "Genetic and molecular approaches have been critical for elucidating the mechanism of the mammalian circadian clock. Here, we demonstrate that the ClockΔ19 mutant behavioral phenotype is significantly modified by mouse strain genetic background. We map a suppressor of the ClockΔ19 mutation to a ~900 kb interval on mouse chromosome 1 and identify the transcription factor, Usf1, as the responsible gene. A SNP in the promoter of Usf1 causes elevation of its transcript and protein in strains that suppress the Clock mutant phenotype. USF1 competes with the CLOCK:BMAL1 complex for binding to E-box sites in target genes. Saturation binding experiments demonstrate reduced affinity of the CLOCKΔ19:BMAL1 complex for E-box sites, thereby permitting increased USF1 occupancy on a genome-wide basis. We propose that USF1 is an important modulator of molecular and behavioral circadian rhythms in mammals.",

author = "Kazuhiro Shimomura and Vivek Kumar and Nobuya Koike and Kim, {Tae Kyung} and Jason Chong and Buhr, {Ethan D.} and Whiteley, {Andrew R.} and Low, {Sharon S.} and Chiaki Omura and Deborah Fenner and Owens, {Joseph R.} and Marc Richards and Yoo, {Seung Hee} and Hong, {Hee Kyung} and Vitaterna, {Martha H.} and Joseph Bass and Pletcher, {Mathew T.} and Tim Wiltshire and John Hogenesch and Lowrey, {Phillip L.} and Takahashi, {Joseph S.}",

year = "2013",

month = apr,

day = "9",

doi = "10.7554/eLife.00426",

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volume = "2013",

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Shimomura, K, Kumar, V, Koike, N, Kim, TK, Chong, J, Buhr, ED, Whiteley, AR, Low, SS, Omura, C, Fenner, D, Owens, JR, Richards, M, Yoo, SH, Hong, HK , Vitaterna, MH , Bass, J, Pletcher, MT, Wiltshire, T, Hogenesch, J, Lowrey, PL & Takahashi, JS 2013, 'Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice', eLife, vol. 2013, no. 2, e00426. https://doi.org/10.7554/eLife.00426

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T1 - Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice

AU - Shimomura, Kazuhiro

AU - Kumar, Vivek

AU - Koike, Nobuya

AU - Kim, Tae Kyung

AU - Chong, Jason

AU - Buhr, Ethan D.

AU - Whiteley, Andrew R.

AU - Low, Sharon S.

AU - Omura, Chiaki

AU - Fenner, Deborah

AU - Owens, Joseph R.

AU - Richards, Marc

AU - Yoo, Seung Hee

AU - Hong, Hee Kyung

AU - Vitaterna, Martha H.

AU - Bass, Joseph

AU - Pletcher, Mathew T.

AU - Wiltshire, Tim

AU - Hogenesch, John

AU - Lowrey, Phillip L.

AU - Takahashi, Joseph S.

PY - 2013/4/9

Y1 - 2013/4/9

N2 - Genetic and molecular approaches have been critical for elucidating the mechanism of the mammalian circadian clock. Here, we demonstrate that the ClockΔ19 mutant behavioral phenotype is significantly modified by mouse strain genetic background. We map a suppressor of the ClockΔ19 mutation to a ~900 kb interval on mouse chromosome 1 and identify the transcription factor, Usf1, as the responsible gene. A SNP in the promoter of Usf1 causes elevation of its transcript and protein in strains that suppress the Clock mutant phenotype. USF1 competes with the CLOCK:BMAL1 complex for binding to E-box sites in target genes. Saturation binding experiments demonstrate reduced affinity of the CLOCKΔ19:BMAL1 complex for E-box sites, thereby permitting increased USF1 occupancy on a genome-wide basis. We propose that USF1 is an important modulator of molecular and behavioral circadian rhythms in mammals.

AB - Genetic and molecular approaches have been critical for elucidating the mechanism of the mammalian circadian clock. Here, we demonstrate that the ClockΔ19 mutant behavioral phenotype is significantly modified by mouse strain genetic background. We map a suppressor of the ClockΔ19 mutation to a ~900 kb interval on mouse chromosome 1 and identify the transcription factor, Usf1, as the responsible gene. A SNP in the promoter of Usf1 causes elevation of its transcript and protein in strains that suppress the Clock mutant phenotype. USF1 competes with the CLOCK:BMAL1 complex for binding to E-box sites in target genes. Saturation binding experiments demonstrate reduced affinity of the CLOCKΔ19:BMAL1 complex for E-box sites, thereby permitting increased USF1 occupancy on a genome-wide basis. We propose that USF1 is an important modulator of molecular and behavioral circadian rhythms in mammals.

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Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice

Abstract

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