Phosphorylation of LSD1 by PKCα Is Crucial for Circadian Rhythmicity and Phase Resetting

Hye Jin Nam, Kyungjin Boo, Dongha Kim, Dong Hee Han, Han Kyoung Choe, Chang Rok Kim, Woong Sun, Hyun Kim, Kyungjin Kim, Ho Lee, Eric Metzger, Roland Schuele, Seung Hee Yoo, Joseph S. Takahashi, Sehyung Cho, Gi Hoon Son, Sung Hee Baek

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46 Citations (Scopus)

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 invivo 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 Lsd1SA/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.

Original languageEnglish
Pages (from-to)791-805
Number of pages15
JournalMolecular Cell
Volume53
Issue number5
DOIs
Publication statusPublished - 2014 Mar 6

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Nam, H. J., Boo, K., Kim, D., Han, D. H., Choe, H. K., Kim, C. R., Sun, W., Kim, H., Kim, K., Lee, H., Metzger, E., Schuele, R., Yoo, S. H., Takahashi, J. S., Cho, S., Son, G. H., & Baek, S. H. (2014). Phosphorylation of LSD1 by PKCα Is Crucial for Circadian Rhythmicity and Phase Resetting. Molecular Cell, 53(5), 791-805. https://doi.org/10.1016/j.molcel.2014.01.028