The progesterone receptor (PR) plays important roles in the establishment and 
maintenance of pregnancy. By dynamic interactions with coregulators, PR 
represses the expression of genes that increase the contractile activity of 
myometrium and contribute to the initiation of labor. We have previously shown 
that PTB-associated RNA splicing factor (PSF) can function as a PR corepressor. 
In this report, we demonstrated that the PSF heterodimer partner, p54nrb 
(non-POU-domain-containing, octamer binding protein), can also function as a 
transcription corepressor, independent of PSF. p54nrb Interacts directly with PR 
independent of progesterone. In contrast to PSF, p54nrb neither enhances PR 
protein degradation nor blocks PR binding to DNA. Rather, p54nrb recruits mSin3A 
through its N terminus to the PR-DNA complex, resulting in an inhibition of 
PR-mediated transactivation of the progesterone-response element-luciferase 
reporter gene. PR also repressed transcription of the connexin 43 gene (Gja1), 
an effect dependent on the presence of an activator protein 1 site within the 
proximal Gja1 promoter. Mutation of this site abolished PR-mediated repression 
and decreased the recruitment of PR and p54nrb onto the Gja1 promoter. 
Furthermore, knockdown p54nrb expression by small interfering RNA alleviated 
PR-mediated repression on Gja1 transcription, whereas overexpression of p54nrb 
enhanced it. In the physiological context of pregnancy, p54nrb protein levels 
decrease with the approach of labor in the rat myometrium. We conclude that 
p54nrb is a transcriptional corepressor of PR. Decreased expression of p54nrb at 
the time of labor may act to derepress PR-mediated inhibition on connexin 43 
expression and contribute to the initiation of labor.