Phosphorylated Bmal1:Clock,Npas2 and coactivators positively regulate expression of Per2

Stable Identifier
R-MMU-9926608
Type
Reaction [omitted]
Species
Mus musculus
Compartment
nucleoplasm, cytosol
ReviewStatus
5/5
General
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Phosphorylated Bmal1:Clock,Npas2 and coactivators positively regulate expression of Per2
Phosphorylated Bmal1:Clock (Arntl:Clock) bound to E-box sequences in the promoter of Per2 drive transcription (Travnickova-Bendova et al. 2002, Rey et al. 2011). Expression of Per2 significantly lags expression of Per1, possibly due to a non-canonical E-box immediately upstream of the first exon of the Per2 gene (Yamajuku et al. 2010). Accumulation of Per2 mRNA begins about 4 hours after phosphorylated Bmal1:Clock binds (Rey et al. 2011) and peaks in the late afternoon of the circadian cycle (Albrechet et al. 1997, Shearman et al. 1997, Takumi et al. 1998, Oishi et al. 2003, Liu et al. 2007). Npas2 can dimerize with Bmal1 and the Bmal1:Npas2 heterodimer binds E-boxes and regulates Per2 expression (Reick et al. 2001, Yoshii et al. 2015).
Literature References
PubMed ID Title Journal Year
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Yoo, SH, Ko, CH, Lowrey, PL, Buhr, ED, Song, EJ, Chang, S, Yoo, OJ, Yamazaki, S, Lee, C, Takahashi, JS

Proc Natl Acad Sci U S A 2005
25526362 Changes in pH and NADPH regulate the DNA binding activity of neuronal PAS domain protein 2, a mammalian circadian transcription factor

Yoshii, K, Tajima, F, Ishijima, S, Sagami, I

Biochemistry 2015
11441147 NPAS2: an analog of clock operative in the mammalian forebrain

Reick, M, Garcia, JA, Dudley, C, McKnight, SL

Science 2001
17994338 Chronobiological analysis of circadian patterns in transcription of seven key clock genes in six peripheral tissues in mice

Liu, S, Cai, Y, Sothern, RB, Guan, Y, Chan, P

Chronobiol Int 2007
12032351 Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity

Travnickova-Bendova, Z, Cermakian, N, Reppert, SM, Sassone-Corsi, P

Proc Natl Acad Sci U S A 2002
9427249 Two period homologs: circadian expression and photic regulation in the suprachiasmatic nuclei

Shearman, LP, Zylka, MJ, Weaver, DR, Kolakowski LF, Jr, Reppert, SM

Neuron 1997
20693532 Identification of functional clock-controlled elements involved in differential timing of Per1 and Per2 transcription

Yamajuku, D, Shibata, Y, Kitazawa, M, Katakura, T, Urata, H, Kojima, T, Nakata, O, Hashimoto, S

Nucleic Acids Res 2010
9619629 A new mammalian period gene predominantly expressed in the suprachiasmatic nucleus

Takumi, T, Matsubara, C, Shigeyoshi, Y, Taguchi, K, Yagita, K, Maebayashi, Y, Sakakida, Y, Okumura, K, Takashima, N, Okamura, H

Genes Cells 1998
12865428 Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes

Oishi, K, Miyazaki, K, Kadota, K, Kikuno, R, Nagase, T, Atsumi, G, Ohkura, N, Azama, T, Mesaki, M, Yukimasa, S, Kobayashi, H, Iitaka, C, Umehara, T, Horikoshi, M, Kudo, T, Shimizu, Y, Yano, M, Monden, M, Machida, K, Matsuda, J, Horie, S, Todo, T, Ishida, N

J Biol Chem 2003
9428527 A differential response of two putative mammalian circadian regulators, mper1 and mper2, to light

Albrecht, U, Sun, ZS, Eichele, G, Lee, CC

Cell 1997
Participants
Input
Output
This event is regulated
Positively by
Regulator
p-S97-Bmal1:p-T451,T461-Clock,p-Npas2:Crebbp:Kmt2a:Per2 gene [nucleoplasm] (Mus musculus)
Active Unit
p-S97-Bmal1:p-T451,T461-Clock,p-Npas2 [nucleoplasm]
Orthologous Events
Phosphorylated BMAL1:CLOCK,NPAS2 and coactivators positively regulate expression of Period-2 (PER2) (Homo sapiens)
Authored
May, B  (2024-11-01)
Reviewed
Sancar, A  (2025-02-14)
Albrecht, U  (2025-02-18)
Created
May, B  (2024-11-01)
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