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Publication : The transcription factors Creb1 and CEBPB regulate Sox9 promoter activity in TM4 Sertoli cells.

First Author  Diawara M Year  2023
Journal  Gene Volume  873
Pages  147477 PubMed ID  37172798
Mgi Jnum  J:336160 Mgi Id  MGI:7487753
Doi  10.1016/j.gene.2023.147477 Citation  Diawara M, et al. (2023) The transcription factors Creb1 and CEBPB regulate Sox9 promoter activity in TM4 Sertoli cells. Gene 873:147477
abstractText  In Sertoli cells, the Sox9 gene is essential for testicular development and normal spermatogenesis. SOX9 is critical for postnatal Sertoli cells differentiation and proliferation in the testis. However, the molecular mechanisms that specifically regulate its expression are not entirely understood. Sox9 expression is regulated by CREB1 and CEBPB in other biological contexts such as during chondrogenesis and in rat thyroid follicular cells. We hypothesized that Sox9 promoter activity is regulated by CREB1 and CEBPB in Sertoli cells. Our results show that Sox9 expression is dependent on the activation of these transcription factors by the cAMP/PKA signaling pathway in TM4 Sertoli cells. Chromatin immunoprecipitation and promoter/reporter luciferase assays with 5' promoter deletions and site-directed mutagenesis demonstrated that CREB1 is being recruited to a DNA regulatory element at -141 bp of the Sox9 promoter region. Such regulation is dependent on the cAMP/PKA signaling pathway, resulting in phosphorylation of CREB1. Activation of Sox9 expression by CEBPB may involve its recruitment to the proximal promoter region by protein-protein interaction with CREB1. Thus, we have shown that the Sox9 promoter is being regulated by the transcription factors CREB1 and CEBPB in TM4 Sertoli cells and involve their recruitment to the proximal promoter region.
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