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Accepted Preprint first posted online on 7 November 2008

Journal of Molecular Endocrinology 2009;42:131.

Journal of Molecular Endocrinology (2008) In press  DOI: 10.1677/JME-08-0016
© 2008 Society for Endocrinology

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Research

Transcriptional cooperation between NF-{kappa}B p50 and C/EBPβ regulates Nur77 transcription in Leydig cells

Bassam El-Asmar, Xavier Giner and Jacques J Tremblay

B El-Asmar, Reproduction, perinatal and child health, CHUL Room T1-49, CHUQ Research Centre, Quebec City, Quebec, Canada
X Giner, Reproduction, perinatal and child health, CHUL Room T1-49, CHUQ Research Centre, Quebec City, Quebec, Canada
J Tremblay, Reproduction, perinatal and child health, CHUL Room T1-49, CHUQ Research Centre, Quebec City, Quebec, Canada

Correspondence: Jacques J Tremblay, Email: Jacques-J.Tremblay{at}crchul.ulaval.ca

Abstract

Expression of steroidogenic enzyme-encoding genes in testicular Leydig cells is complex and involves several transcription factors including the orphan nuclear receptor NUR77 (NR4A1) and the bZIP factor C/EBPβ. How these transcription factors are integrated into a functional network, however, remains to be fully understood. Here we report that the transcription factor C/EBPβ can activate the Nur77 promoter as revealed by transient transfections in MA-10 Leydig cells. Through 5' progressive deletions and site-directed mutagenesis, the C/EBPβ-mediated activation of the Nur77 promoter was found to be dependent on a novel species-conserved C/EBP element located at -110 bp. We also demonstrate using electromobility shift assay that C/EBPβ specifically binds to this element. Furthermore, we report a functional cooperation between C/EBPβ and the p50 subunit of NF-{kappa}B that involves a previously uncharacterized {kappa}B element located at -18 bp. Promoter analysis revealed that either the C/EBP or the {kappa}B element was sufficient to sustain the C/EBPβ-p50 cooperation thus suggesting that both factors physically interact. Altogether, our results provide new data regarding Nur77 transcription in testicular Leydig cells in addition to providing new insights into the interplay between transcription factors involved in Leydig cell gene expression and function.




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J AndrolHome page
L. J. Martin, N. Boucher, B. El-Asmar, and J. J. Tremblay
cAMP-Induced Expression of the Orphan Nuclear Receptor Nur77 in MA-10 Leydig Cells Involves a CaMKI Pathway
J Androl, March 1, 2009; 30(2): 134 - 145.
[Abstract] [Full Text] [PDF]




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