EGR2 is a gonadotropin-induced survival factor that controls the expression of IER3 in ovarian granulosa cells

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• 作者：Hanyong Jin^a ; ¹ ; Miae Won^b ; ¹ ; Eunkyoung Shin^a ; Hong-Man Kim^c ; Kangseok Lee^c ; Jeehyeon Bae^a ; ^{jeehyeon@cau.ac.kr}
• 关键词：KROX20 ; FSH ; LH ; Transcriptional regulation ; Target gene
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2017
• 出版时间：22 January 2017
• 年：2017
• 卷：482
• 期：4
• 页码：877-882
• 全文大小：993 K
• 卷排序：482

文摘

Pituitary gonadotropins are key hormones that orchestrate the growth and development of ovarian follicles. However, limited information is available on intra-ovarian factors that mediate the actions of gonadotropins. In this study, we identified that the early growth response 2 gene (EGR2) is a gonadotropin-inducible gene in granulosa cells of rats and humans. Analysis of consensus EGR-binding elements (EBEs) showed that the immediate early response 3 gene (IER3) is a novel transcriptional target gene of EGR2 as confirmed by the luciferase assay, electrophoretic mobility-shift assay (EMSA), chromatin immunoprecipitation (ChIP), and western blot analysis. Overexpression of EGR2 promoted survival of KGN human granulosa-derived cells in which IER3 acts as a mediator; knockdown of EGR2 induced death in KGN cells. Additionally, EGR2 was found to regulate the expression of myeloid cell leukemia 1 (MCL-1), which belongs to the BCL-2 family of proteins regulating cell survival. Thus, this study identified a novel signaling axis, comprised of gonadotropins-EGR2-IER3, which is important for the survival of granulosa cells during folliculogenesis.