Sumoylation controls CLOCK-BMAL1-mediated clock resetting via CBP recruitment in nuclear transcriptional foci

Yool Lee; Sung Kook Chun; Kyungjin Kim

doi:10.1016/j.bbamcr.2015.07.005

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Sumoylation controls CLOCK-BMAL1-mediated clock resetting via CBP recruitment in nuclear transcriptional foci

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Sumoylation controls CLOCK-BMAL1-mediated clock resetting via CBP recruitment in nuclear transcriptional foci

Yool Lee, Sung Kook Chun and Kyungjin Kim

Biochimica et biophysica acta. Molecular cell research, Vol.1853(10), pp.2697-2708

10/2015

DOI: https://doi.org/10.1016/j.bbamcr.2015.07.005

PMID: 26164627

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Abstract

BiFC-based FRET

BMAL1

CBP

Circadian clock

Clock resetting

Nuclear body

Sumoylation

SUSP1

CLOCK-BMAL1 is a key transcription factor complex of the molecular clock system that generates circadian gene expression and physiology in mammals. Here, we demonstrate that sumoylation of BMAL1 mediates the rapid activation of CLOCK-BMAL1 by CREB-binding protein (CBP) in nuclear foci and also the resetting of the circadian clock. Under physiological conditions, a bimolecular fluorescence complementation-based fluorescence resonance energy transfer (BiFC-FRET) assay revealed that CLOCK-BMAL1 rapidly dimerized and formed a ternary complex with CBP in discrete nuclear foci in response to serum stimuli. We found that the formation of this ternary complex requires sumoylation of BMAL1 by SUMO3. These processes were abolished by both the ectopic expression of the SUMP2/3-specific protease, SUSP1, and mutation of the major sumoylation site (Lys259) of BMAL1. Moreover, molecular inhibition of BMAL1 sumoylation abrogated acute Per1 transcription and severely dampened the circadian gene oscillation triggered by clock synchronization stimuli. Taken together, these findings suggest that sumoylation plays a critical role in the spatiotemporal co-activation of CLOCK-BMAL1 by CBP for immediate-early Per induction and the resetting of the circadian clock. •BiFC-FRET analysis visualizes CLOCK/BMAL1/CBP ternary complex formation in nuclear transcriptional foci.•Rapid sumoylation of BMAL1 mediates stimuli-induced CLOCK/BMAL1/CBP complex formation in nuclear bodies.•BMAL1 sumoylation regulates CBP co-activation of CLOCK-BMAL1-mediated circadian clock resetting.

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Title: Sumoylation controls CLOCK-BMAL1-mediated clock resetting via CBP recruitment in nuclear transcriptional foci
Creators: Yool Lee - Washington State University, Biomedical Sciences, Department of
Sung Kook Chun - Daegu Gyeongbuk Institute of Science and Technology
Kyungjin Kim - Daegu Gyeongbuk Institute of Science and Technology
Publication Details: Biochimica et biophysica acta. Molecular cell research, Vol.1853(10), pp.2697-2708
Academic Unit: Elson S. Floyd College of Medicine
Publisher: Elsevier B.V
Identifiers: 99901132535401842
Language: English
Resource Type: Journal article