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Phosphorylation of LSD1 by PKCα is crucial for circadian rhythmicity and phase resetting.

Abstract：

:The circadian clock is a self-sustaining oscillator that controls daily rhythms. For the proper circadian gene expression, dynamic changes in chromatin structure are important. Although chromatin modifiers have been shown to play a role in circadian gene expression, the in vivo role of circadian signal-modulated chromatin modifiers at an organism level remains to be elucidated. Here, we provide evidence that the lysine-specific demethylase 1 (LSD1) is phosphorylated by protein kinase Cα (PKCα) in a circadian manner and the phosphorylated LSD1 forms a complex with CLOCK:BMAL1 to facilitate E-box-mediated transcriptional activation. Knockin mice bearing phosphorylation-defective Lsd1(SA/SA) alleles exhibited altered circadian rhythms in locomotor behavior with attenuation of rhythmic expression of core clock genes and impaired phase resetting of circadian clock. These data demonstrate that LSD1 is a key component of the molecular circadian oscillator, which plays a pivotal role in rhythmicity and phase resetting of the circadian clock.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Nam HJ,Boo K,Kim D,Han DH,Choe HK,Kim CR,Sun W,Kim H,Kim K,Lee H,Metzger E,Schuele R,Yoo SH,Takahashi JS,Cho S,Son GH,Baek SH

doi

10.1016/j.molcel.2014.01.028

subject

Has Abstract

pub_date

2014-03-06 00:00:00

pages

791-805

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(14)00111-7

journal_volume

53

pub_type

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