KLF6 cooperates with NUR77 and SF1 to activate the human INSL3 promoter in mouse MA-10 leydig cells
| Autor: | Raifish E Mendoza-Villarroel, Francis Bergeron, Maxime A Tremblay, Jacques J. Tremblay, Nicholas M. Robert |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Transcriptional Activation endocrine system Nerve growth factor IB Kruppel-Like Transcription Factors 030209 endocrinology & metabolism Biology Regulatory Sequences Nucleic Acid Response Elements Cell Line 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Transcription (biology) Proto-Oncogene Proteins Testis Transcriptional regulation medicine Kruppel-Like Factor 6 Nuclear Receptor Subfamily 4 Group A Member 1 Animals Humans Insulin Promoter Regions Genetic Molecular Biology Transcription factor Genetics Binding Sites Chromosome Mapping Leydig Cells Proteins Sertoli cell Cell biology Blot 030104 developmental biology KLF6 medicine.anatomical_structure Nuclear receptor Gene Expression Regulation RNA Splicing Factors Protein Binding |
| Zdroj: | Journal of molecular endocrinology. 56(3) |
| ISSN: | 1479-6813 |
| Popis: | Insulin-like 3 (INSL3), a Leydig cell-specific hormone, is essential for testis descent during foetal life and bone metabolism in adults. Despite its essential roles in male reproductive and bone health, very little is known regarding its transcriptional regulation in Leydig cells. To date, few transcription factors have been shown to activateINSL3promoter activity: the nuclear receptors AR, NUR77, COUP-TFII and SF1. To identify additional regulators, we have isolated and performed a detailed analysis of a 1.1 kb humanINSL3promoter fragment. Through 5′ progressive deletions and site-directed mutagenesis, we have mapped a 10 bp element responsible for about 80% ofINSL3promoter activity in Leydig cells. This element is identical to the CPE element of the placental-specific glycoprotein-5 (PSG5) promoter that is recognized by the developmental regulator Krüppel-like factor 6 (KLF6). Using PCR and western blotting, we found that KLF6 is expressed in several Leydig and Sertoli cell lines. Furthermore, immunohistochemistry on adult mouse testis revealed the presence of KLF6 in the nuclei of both Leydig and Sertoli cells. KLF6 binds to the 10 bp KLF element at −108 bp and activates the −1.1 kb human, but not the mouse,INSL3promoter. KLF6-mediated activation of the humanINSL3promoter required an intact KLF element as well as Leydig/Sertoli-enriched factors because KLF6 did not stimulate the humanINSL3promoter activity in CV-1 fibroblast cells. Consistent with this, we found that KLF6 transcriptionally cooperates with NUR77 and SF1. Collectively, our results identify KLF6 as a regulator of humanINSL3transcription. |
| Databáze: | OpenAIRE |
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