As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) and BMAL1:NPAS2 (ARNTL:NPAS2) heterodimers bind to sequence elements (E boxes) in the promoters of target genes and enhance transcription (Gekakis et al. 1998, reviewed in Munoz and Baler 2003).
View original pathway at Reactome.
Li R, Yue J, Zhang Y, Zhou L, Hao W, Yuan J, Qiang B, Ding JM, Peng X, Cao JM.; ''CLOCK/BMAL1 regulates human nocturnin transcription through binding to the E-box of nocturnin promoter.''; PubMedEurope PMCScholia
Mukherjee R, Jow L, Noonan D, McDonnell DP.; ''Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators.''; PubMedEurope PMCScholia
Muñoz E, Baler R.; ''The circadian E-box: when perfect is not good enough.''; PubMedEurope PMCScholia
Greenberg D, Miao CH, Ho WT, Chung DW, Davie EW.; ''Liver-specific expression of the human factor VII gene.''; PubMedEurope PMCScholia
Maemura K, de la Monte SM, Chin MT, Layne MD, Hsieh CM, Yet SF, Perrella MA, Lee ME.; ''CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression.''; PubMedEurope PMCScholia
Rakhshandehroo M, Hooiveld G, Müller M, Kersten S.; ''Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.''; PubMedEurope PMCScholia
Chong NW, Codd V, Chan D, Samani NJ.; ''Circadian clock genes cause activation of the human PAI-1 gene promoter with 4G/5G allelic preference.''; PubMedEurope PMCScholia
Fisch S, Gray S, Heymans S, Haldar SM, Wang B, Pfister O, Cui L, Kumar A, Lin Z, Sen-Banerjee S, Das H, Petersen CA, Mende U, Burleigh BA, Zhu Y, Pinto YM, Liao R, Jain MK.; ''Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy.''; PubMedEurope PMCScholia
Tamaru T, Hirayama J, Isojima Y, Nagai K, Norioka S, Takamatsu K, Sassone-Corsi P.; ''CK2alpha phosphorylates BMAL1 to regulate the mammalian clock.''; PubMedEurope PMCScholia
van der Bom JG, Bots ML, Haverkate F, Kluft C, Grobbee DE.; ''The 4G5G polymorphism in the gene for PAI-1 and the circadian oscillation of plasma PAI-1.''; PubMedEurope PMCScholia
Schoenhard JA, Smith LH, Painter CA, Eren M, Johnson CH, Vaughan DE.; ''Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2.''; PubMedEurope PMCScholia
Hagen FS, Gray CL, O'Hara P, Grant FJ, Saari GC, Woodbury RG, Hart CE, Insley M, Kisiel W, Kurachi K.; ''Characterization of a cDNA coding for human factor VII.''; PubMedEurope PMCScholia
Thim L, Bjoern S, Christensen M, Nicolaisen EM, Lund-Hansen T, Pedersen AH, Hedner U.; ''Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells.''; PubMedEurope PMCScholia
Muñoz E, Brewer M, Baler R.; ''Circadian Transcription. Thinking outside the E-Box.''; PubMedEurope PMCScholia
Juge-Aubry C, Pernin A, Favez T, Burger AG, Wahli W, Meier CA, Desvergne B.; ''DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5'-flanking region.''; PubMedEurope PMCScholia
Ognjanovic S, Bao S, Yamamoto SY, Garibay-Tupas J, Samal B, Bryant-Greenwood GD.; ''Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes.''; PubMedEurope PMCScholia
Oishi K, Shirai H, Ishida N.; ''CLOCK is involved in the circadian transactivation of peroxisome-proliferator-activated receptor alpha (PPARalpha) in mice.''; PubMedEurope PMCScholia
Khatib ZA, Inaba T, Valentine M, Look AT.; ''Chromosomal localization and cDNA cloning of the human DBP and TEF genes.''; PubMedEurope PMCScholia
Sausville E, Carney D, Battey J.; ''The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line.''; PubMedEurope PMCScholia
Fujimoto K, Shen M, Noshiro M, Matsubara K, Shingu S, Honda K, Yoshida E, Suardita K, Matsuda Y, Kato Y.; ''Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins.''; PubMedEurope PMCScholia
Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, Weitz CJ.; ''Role of the CLOCK protein in the mammalian circadian mechanism.''; PubMedEurope PMCScholia
Dardente H, Fortier EE, Martineau V, Cermakian N.; ''Cryptochromes impair phosphorylation of transcriptional activators in the clock: a general mechanism for circadian repression.''; PubMedEurope PMCScholia
Kawamoto T, Noshiro M, Sato F, Maemura K, Takeda N, Nagai R, Iwata T, Fujimoto K, Furukawa M, Miyazaki K, Honma S, Honma Ki, Kato Y.; ''A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation.''; PubMedEurope PMCScholia
MED1 is a component of each of the various Mediator complexes, that function as transcription co-activators. The MED1-containing compolexes include the DRIP, ARC, TRIP and CRSP compllexes.
Peroxisome proliferator receptor elements bind heterodimers containing a peroxisome proliferator receptor and a retinoic acid receptor. The consensus sequence is TGAMCTTTGNCCTAGWTYYG.
The NAMPT (NamPRT) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer enhances transcription of NAMPT.
The PAI-1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein. The PAI-1 gene shows circadian expression due to direct transcriptional activation by the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer and the BMAL2:CLOCK (CLIF:CLOCK, ARNTL2:CLOCK) heterodimer.
The NOCTURNIN gene is transcribed to yield mRNA and the mRNA is translated to yield protein. The NOCTURNIN gene shows circadian expression because the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds an E-box element in the NOCTURNIN promoter and activates transcription.
The FACTOR VII (F7) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. In mouse the F7 gene shows circadian expression due to activation by the Bmal1:Clock (Arntl:Clock) heterodimer.
As inferred from mouse, the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds E-box elements in the promoter of the DEC2 (BHLHE41, BHLHB3) gene and activates transcription of DEC2.
The phosphorylated BMAL1:CLOCK (ARNTL) heterodimer binds an E-box in the promoter of the PAI-1 gene and activate transcription of PAI-1. NPAS2 is predicted to act redundantly with CLOCK.
Activation of FACTOR VII expression by phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) is inferred from mouse. NPAS2 is predicted to act redundantly with CLOCK.
The phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds an E-box element in the promoter of the NOCTURNIN gene and activates transcription of NOCTURNIN. NPAS2 is predicted to act redundantly with CLOCK.
As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind E-boxes in the second intron of the PPARA gene and activate transcription of PPARA.
The PPARA gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind the scond intron of the PPARA gene and activate transcription of PPARA.
The DBP gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind E-boxes in the DBP promoter and activate transcription of DBP.
The DEC2 (BHLHE41, BHLHB3) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds E-box elements in the DEC2 promoter and activates transcription of DEC2.
The AVP gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind an E-box enhancer in the promoter of the AVP gene and activate transcription of AVP.
The DEC1 (BHLHE40, BHLHB2) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. The DEC1 gene contains E-box elements in its promoter which bind the BMAL:CLOCK (ARNTL:CLOCK) heterodimer and confer circadian rhythm on its expression.
The KLF15 gene is transcribed to yield mRNA and the mRNA is translated to yield protein. Transcription of KLF15 exhibits a circadian rhythm due to regulation by BMAL1:CLOCK (inferred from mouse homologs).
The BMAL1:CLOCK heterodimer binds E-boxes in the promoter of the KLF15 gene and activates transcription (inferred from mouse homologs). KLF15 then regulates cardiac ion-channel expression and QT-interval duration (inferred from mouse homologs).
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