title: 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.
authors.affiliation: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Nam
authors.affiliation: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Boo
authors.affiliation: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Dongha
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Neuroscience, Neurodegeneration Control Research Center, Kyung Hee University School of Medicine, Seoul 130-701, South Korea.
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Han
authors.affiliation: Brain Research Center for the 21st Frontier Program in Neuroscience, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Han Kyoung
authors.initials: HK
authors.lastname: Choe
authors.affiliation: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Chang Rok
authors.initials: CR
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-705, South Korea.
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-705, South Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Brain Research Center for the 21st Frontier Program in Neuroscience, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Kim
authors.affiliation: Division of Basic and Applied Sciences, National Cancer Center, Gyeonggi-do 410-769, South Korea.
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, DKTK Standort Freiburg, BIOSS Centre of Biological Signaling Studies, Albert-Ludwigs-University, 79106 Freiburg, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Metzger
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, DKTK Standort Freiburg, BIOSS Centre of Biological Signaling Studies, Albert-Ludwigs-University, 79106 Freiburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schuele
authors.affiliation: Howard Hughes Medical Institute, Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Yoo
authors.affiliation: Howard Hughes Medical Institute, Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Takahashi
authors.affiliation: Department of Neuroscience, Neurodegeneration Control Research Center, Kyung Hee University School of Medicine, Seoul 130-701, South Korea.
authors.forename: Sehyung
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Legal Medicine, Korea University College of Medicine, Seoul 136-705, South Korea.
authors.forename: Gi Hoon
authors.initials: GH
authors.lastname: Son
authors.affiliation: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea. Electronic address: sbaek@snu.ac.kr.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Baek
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal; D056926:CLOCK Proteins / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D002940:Circadian Rhythm; D005786:Gene Expression Regulation; D056466:Histone Demethylases; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009991:Oscillometry; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D013997:Time Factors
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D010089:Oxidoreductases, N-Demethylating; D056926:CLOCK Proteins; C538944:Clock protein, mouse; C496630:Prkca protein, mouse; D051571:Protein Kinase C-alpha