The tissue-specific transcription factor Pit-1/GHF-1 binds to the c-fos serum response element and activates c-fos transcription.
Pit-1, a POU domain-containing transcription factor, is involved in two functions in the pituitary: PRL and GH tissue-specific expression and somatolactotroph cells expansion. To analyze the molecular basis of the latter function, we tested whether Pit-1 can directly transactivate expression of an early marker of cell cycle initiation, the c-fos gene. We show that Pit-1 overexpression in PC12 cells, which do not express Pit-1, increases c-fos expression. Moreover, cAMP-induced c-fos promoter activity is decreased in the somatolactotroph cell line GH3 when Pit-1 expression is reduced by hybrid arrest with an antisense sequence complementary to Pit-1 cDNA. In contrast to hormonal genes regulation, where it has been shown that any Pit-1 phosphorylation site is involved, we show that the Pit-1 phosphorylation sites are required to allow increase of c-fos promoter activity by Pit-1. We further show, by gel shift analyses, that Pit-1 is able to specifically bind the serum response element sequence present within the c-fos promoter but with a lesser affinity than the Pit-1 response element. Taken together, these results demonstrate that the tissue-specific transcription factor Pit-1 is able to enhance expression of genes involved in cell cycle initiation, suggesting that this mechanism allows Pit-1 to increase somato-lactotroph cell proliferation.
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D016716:PC12 Cells / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic