FOXL2 Interacts with Steroidogenic Factor-1 (SF-1) and Represses SF-1-Induced CYP17 Transcription in Granulosa Cellsopen access
- Authors
- Park, Mira; Shin, Eunkyoung; Won, Miae; Kim, Jae-Hong; Go, Hayoung; Kim, Hyun-Lee; Ko, Jeong-Jae; Lee, Kangseok; Bae, Jeehyeon
- Issue Date
- May-2010
- Publisher
- ENDOCRINE SOC
- Citation
- MOLECULAR ENDOCRINOLOGY, v.24, no.5, pp 1024 - 1036
- Pages
- 13
- Journal Title
- MOLECULAR ENDOCRINOLOGY
- Volume
- 24
- Number
- 5
- Start Page
- 1024
- End Page
- 1036
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/22470
- DOI
- 10.1210/me.2009-0375
- ISSN
- 0888-8809
- Abstract
- Mutations in FOXL2 are responsible for blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) type I, in which affected women exhibit premature ovarian failure. FOXL2-null mice showed defects in granulosa cell development during folliculogenesis. We screened a rat ovarian yeast two-hybrid cDNA library to identify FOXL2-interacting proteins and found steroidogenic factor-1 (SF-1). Here, we show that human FOXL2 and SF-1 proteins interact in human granulosa cells and that FOXL2 negatively regulates the transcriptional activation of a steroidogenic enzyme, CYP17, by SF-1. Furthermore, FOXL2 mutants found in blepharophimosis-ptosis-epicanthus inversus syndrome type I patients lost the ability to repress CYP17 induction mediated by SF-1. Chromatin immunoprecipitation and EMSA results further revealed that FOXL2 inhibited the binding of SF-1 to the CYP17 promoter, whereas the FOXL2 mutants failed to block this interaction. Therefore, this study identifies a novel regulatory role for FOXL2 on a key steroidogenic enzyme and provides a possible mechanism by which mutations in FOXL2 disrupt normal ovarian follicle development. (Molecular Endocrinology 24: 1024-1036, 2010)
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