Synergistic activation of the Mc2r promoter by FOXL2 and NR5A1 in mice.

Biology of Reproduction
Wei-Hsiung YangChiung-Min Wang

Abstract

Forkhead box protein L2 (FOXL2) is the earliest ovarian marker and plays an important role in the regulation of cholesterol and steroid metabolism, inflammation, apoptosis, and ovarian development and function. Mutations and deficiencies of the human FOXL2 gene have been shown to cause blepharophimosis-ptosis-epicanthus inversus syndrome as well as premature ovarian failure. Although Foxl2 interacts with steroidogenic factor 1 (Nr5a1) and up-regulates cyp19a1a gene transcription in fish, FOXL2 represses the transcriptional activity of the gene that codes for steroidogenic acute regulatory protein (Star) in mice. Most of the recent studies have heavily focused on the FOXL2 target genes (Star and Cyp19a1) in the ovaries. Hence, it is of importance to search for other downstream targets of FOXL2 and for the possibility of FOXL2 expression in nonovarian tissues. Herein, we demonstrate that the interplay between FOXL2 and NR5A1 regulates Star and melanocortin 2 receptor (Mc2r) gene expression in mammalian systems. Both FOXL2 and NR5A1 are expressed in ovarian and adrenal gland tissues. As expected, FOXL2 represses and NR5A1 enhances the promoter activity of Star. Notably, the promoter activity of Mc2r is activated by FOXL2 in a dose...Continue Reading

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Citations

Oct 6, 2012·Sexual Development : Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation·A Bashamboo, K McElreavey
Nov 16, 2013·International Journal of Molecular Sciences·Chiung-Min WangWei-Hsiung Yang
Jul 19, 2011·Molecular and Cellular Endocrinology·Sandrine CaburetReiner A Veitia
Oct 8, 2014·Molecular and Cellular Endocrinology·Maximiliaan SchillebeeckxDavid B Wilson
Feb 2, 2017·International Journal of Molecular Sciences·Chiung-Min WangWei-Hsiung Yang
Oct 18, 2016·Scientific Reports·Laura CasasXabier Irigoien
Feb 22, 2013·Biology of Reproduction·Daniel J Bernard, Stella Tran
Jan 31, 2020·Frontiers in Endocrinology·Esdras da Silva Oliveira BarbosaSilvina R Villar
Nov 13, 2019·Nature Communications·Barbara NicolHumphrey H-C Yao

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Methods Mentioned

BETA
Assay
PCR
two-hybrid
Transfection
pull-down
protein assay
electrophoresis
coimmunoprecipitation assay
coimmunoprecipitation

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