Phosphorylated BMAL1:CLOCK,NPAS2 and coactivators positively regulate expression of Period-1 (PER1)

Stable Identifier
R-HSA-9909561
Type
Reaction [uncertain]
Species
Homo sapiens
Compartment
nucleoplasm, cytosol
ReviewStatus
5/5
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Phosphorylated BMAL1:CLOCK,NPAS2 and coactivators positively regulate expression of Period-1 (PER1)
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In the nucleus, CIPC binds CLOCK in the CLOCK:BMAL1 complex (inferred from mouse homologs in Zhao et al. 2007), enhances phosphorylation of CLOCK (inferred from mouse homologs in Yoshitane et al. 2009), and represses transcriptional activation of the PER1 gene by CLOCK:BMAL1 (inferred from mouse homologs in Zhao et al. 2007, Qu et al. 2015). As inferred from mouse homologs, RBM4 (hLARK) binds the 3' UTR of PER1 mRNA and increases production of PER1 protein probably by enhancing translation (Kojima et al. 2007). Phosphorylated BMAL1:CLOCK heterodimers bound to four (inferred from mouse homologs) or five (Hida et al. 2000) E-boxes in the PER1 promoter additively transactivate transcription (Hida et al. 2000). Expression of PER1 in cell culture is inducible by serum and oscillates in a circadian rhythm (Miyazaki et al. 2004). In the suprachiasmatic nucleus (inferred from mice) and other regions of the brain (Li et al. 2013), expression of PER1 peaks early in the day (Li et al. 2013). NPAS2 can heterodimerize with BMAL1 in place of CLOCK and the heterodimer activates expression of PER1 (inferred from mouse homologs). As inferred from mouse homologs, the ICER isoform of CREM ( binds cAMP-responsive elements in the PER1 promoter and represses transcription of PER1 (Zmrzljak et al. 2013). Other isoforms of CREM may also repress PER1. DEC1 (BHLHE40) negatively regulates transcription of PER1 by binding an E-box element in the PER1 promoter and interacting with the transcription factor Sp1 (inferred from mouse homologs in Li et al. 2004).
Literature References
PubMed ID Title Journal Year
23671070 Circadian patterns of gene expression in the human brain and disruption in major depressive disorder

Li, JZ, Bunney, BG, Meng, F, Hagenauer, MH, Walsh, DM, Vawter, MP, Evans, SJ, Choudary, PV, Cartagena, P, Barchas, JD, Schatzberg, AF, Jones, EG, Myers, RM, Watson, SJ, Akil, H, Bunney, WE

Proc Natl Acad Sci U S A 2013
10857746 The human and mouse Period1 genes: five well-conserved E-boxes additively contribute to the enhancement of mPer1 transcription

Hida, A, Koike, N, Hirose, M, Hattori, M, Sakaki, Y, Tei, H

Genomics 2000
14750904 Phosphorylation of clock protein PER1 regulates its circadian degradation in normal human fibroblasts

Miyazaki, K, Nagase, T, Mesaki, M, Narukawa, J, Ohara, O, Ishida, N

Biochem J 2004
17994337 Activation of human period-1 by PKA or CLOCK/BMAL1 is conferred by separate signal transduction pathways

Motzkus, D, Loumi, S, Cadenas, C, Vinson, C, Forssmann, WG, Maronde, E

Chronobiol Int 2007
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
SIK1 [nucleoplasm] (Homo sapiens)
Regulator
BHLHE40 dimer [nucleoplasm] (Homo sapiens)
Regulator
p-S-BMAL1:p-S-CLOCK:CIPC [nucleoplasm] (Homo sapiens)
Active Unit
CIPC [nucleoplasm]
Regulator
CREM:PER1 gene [nucleoplasm] (Homo sapiens)
Positively by
Regulator
p-CREB:CRTC1:PER1 gene [nucleoplasm] (Homo sapiens)
Regulator
RBM4:PER1 mRNA [cytosol] (Homo sapiens)
Regulator
p-S90-BMAL1:p-T451,T461-CLOCK,p-NPAS2:CREBBP:KMT2A:PER1 gene [nucleoplasm] (Homo sapiens)
Active Unit
p-S90-BMAL1:p-T451,T461-CLOCK,p-NPAS2 [nucleoplasm]
Inferred From
Phosphorylated Bmal1:Clock,Npas2 and coactivators positively regulate expression of Period-1 (Per1) (Mus musculus)
Authored
May, B  (2024-05-14)
Reviewed
Sancar, A  (2025-02-14)
Albrecht, U  (2025-02-18)
Created
May, B  (2024-05-14)
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