bims-ciryme 2019-07-14 papers

on Circadian rhythms and metabolism

Issue of 2019–07–14
two papers selected by
Gabriela Da Silva Xavier, University of Birmingham

Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters.
Circadian biology and sleep in monogenic neurological disorders and its potential application in drug discovery.

Elife. 2019 Jul 11. pii: e43235. [Epub ahead of print]8

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

Nikolai Petkau, Harun Budak, Xunlei Zhou, Henrik Oster, Gregor Eichele.

  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.

Keywords:  chromosomes; gene expression; mouse; neuroscience

DOI:  https://doi.org/10.7554/eLife.43235
Curr Opin Behav Sci. 2019 Feb;25 23-30

Circadian biology and sleep in monogenic neurological disorders and its potential application in drug discovery.

Shu-Qun Shi, Carl Hirschie Johnson.

Sleep disturbances are common in people with monogenic neurological disorders and they dramatically affect the life of individuals with the disorders and their families. The associated sleep problems are probably caused by multiple factors that have not been elucidated. Study of the underlying molecular cause, behavioral phenotypes, and reciprocal interactions in several single-gene disorders (Angelman Syndrome, Fragile X Syndrome, Rett Syndrome, and Huntington's Disease) leads to the suggestion that sleep disruption and other symptoms may directly result from abnormal operation of circadian systems due to genetic alteration and/or conflicting environmental cues for clock entrainment. Therefore, because circadian patterns modify the symptoms of neurological disorders, treatments that modulate our daily rhythms may identify heretofore unappreciated therapies for the underlying disorders.

DOI: https://doi.org/10.1016/j.cobeha.2018.06.006