25-02-2018, 04:02 AM
interesting: FoxL2 is expressed in adrenal glands as well(in mice):
http://www.bioone.org/doi/10.1095/biolreprod.110.085621?prevSearch=
Synergistic Activation of the [i]Mc2r[/i] Promoter by FOXL2 and NR5A1 in Mice[url=http://www.bioone.org/doi/10.1095/biolreprod.110.085621?prevSearch=#n104][/url]
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 [i]FOXL2[/i] 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 [i]cyp19a1a[/i] gene transcription in fish, FOXL2 represses the transcriptional activity of the gene that codes for steroidogenic acute regulatory protein ([i]Star[/i]) in mice. Most of the recent studies have heavily focused on the FOXL2 target genes ([i]Star[/i] and [i]Cyp19a1[/i]) 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 [i]Star[/i] and melanocortin 2 receptor ([i]Mc2r[/i]) 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 [i]Star[/i]. Notably, the promoter activity of [i]Mc2r[/i] is activated by FOXL2 in a dose-dependent manner. Surprisingly, we found that FOXL2 and NR5A1 synergistically up-regulate the transcriptional activity of [i]Mc2r[/i]. By mapping the [i]Mc2r[/i] promoter, we provide evidence that distal NR5A1 response elements (−1410 and −975) are required for synergistic activation by FOXL2 and NR5A1. These results suggest that the interplay between FOXL2 and NR5A1 on the [i]Mc2r[/i] promoter functions as a novel mechanism for regulating MC2R-mediated cell signaling as well as steroidogenesis in adrenal glands.
http://www.bioone.org/doi/10.1095/biolreprod.110.085621?prevSearch=
Synergistic Activation of the [i]Mc2r[/i] Promoter by FOXL2 and NR5A1 in Mice[url=http://www.bioone.org/doi/10.1095/biolreprod.110.085621?prevSearch=#n104][/url]
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 [i]FOXL2[/i] 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 [i]cyp19a1a[/i] gene transcription in fish, FOXL2 represses the transcriptional activity of the gene that codes for steroidogenic acute regulatory protein ([i]Star[/i]) in mice. Most of the recent studies have heavily focused on the FOXL2 target genes ([i]Star[/i] and [i]Cyp19a1[/i]) 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 [i]Star[/i] and melanocortin 2 receptor ([i]Mc2r[/i]) 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 [i]Star[/i]. Notably, the promoter activity of [i]Mc2r[/i] is activated by FOXL2 in a dose-dependent manner. Surprisingly, we found that FOXL2 and NR5A1 synergistically up-regulate the transcriptional activity of [i]Mc2r[/i]. By mapping the [i]Mc2r[/i] promoter, we provide evidence that distal NR5A1 response elements (−1410 and −975) are required for synergistic activation by FOXL2 and NR5A1. These results suggest that the interplay between FOXL2 and NR5A1 on the [i]Mc2r[/i] promoter functions as a novel mechanism for regulating MC2R-mediated cell signaling as well as steroidogenesis in adrenal glands.