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  Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters.

Petkau, N., Budak, H., Zhou, X., Oster, H., & Eichele, G. (2019). Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters. eLife, 8: e43235. doi:10.7554/eLife.43235.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-4278-B Version Permalink: http://hdl.handle.net/21.11116/0000-0004-6357-B
Genre: Journal Article

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 Creators:
Petkau, N.1, Author              
Budak, H., Author
Zhou, X., Author
Oster, H., Author
Eichele, G.1, Author              
Affiliations:
1Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society, ou_persistent34              

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Free keywords: Many physiological processes exhibit circadian rhythms driven by cellular clocks composed of interlinked activating and repressing elements. To investigate temporal regulation in this molecular oscillator, we combined mouse genetic approaches and analyses of interactions of key circadian proteins with each other and with clock gene promoters. We show that transcriptional activators control BRD4-PTEFb recruitment to E-box-containing circadian promoters. During the activating phase of the circadian cycle, the lysine acetyltransferase TIP60 acetylates the transcriptional activator BMAL1 leading to recruitment of BRD4 and the pause release factor P-TEFb, followed by productive elongation of circadian transcripts. We propose that the control of BRD4-P-TEFb recruitment is a novel temporal checkpoint in the circadian clock cycle.
 Abstract: Many physiological processes exhibit circadian rhythms driven by cellular clocks composed of interlinked activating and repressing elements. To investigate temporal regulation in this molecular oscillator, we combined mouse genetic approaches and analyses of interactions of key circadian proteins with each other and with clock gene promoters. We show that transcriptional activators control BRD4-PTEFb recruitment to E-box-containing circadian promoters. During the activating phase of the circadian cycle, the lysine acetyltransferase TIP60 acetylates the transcriptional activator BMAL1 leading to recruitment of BRD4 and the pause release factor P-TEFb, followed by productive elongation of circadian transcripts. We propose that the control of BRD4-P-TEFb recruitment is a novel temporal checkpoint in the circadian clock cycle.

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Language(s): eng - English
 Dates: 2019-07-11
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.7554/eLife.43235
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Title: eLife
Source Genre: Journal
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Pages: 20 Volume / Issue: 8 Sequence Number: e43235 Start / End Page: - Identifier: -