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 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.
BMAL2 (ARNTL2, CLIF) forms a heterodimer with CLOCK, binds E-boxes in the PAI-1 promoter and activates transcription of the PAI-1 gene. BMAL2 shows constitutive rather than circadian expression.