NCBI Summary:
The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F2 and E2F3, have an additional cyclin binding domain. This protein binds preferentially to retinoblastoma protein pRB in a cell-cycle dependent manner. It can mediate both cell proliferation and p53-dependent/independent apoptosis. [provided by RefSeq, Jul 2008]
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Steroid metabolism
Comment
Regulation of the transcription factor E2F1 mRNA in ovarian granulosa cells of cattle. Morrell BC et al. (2019) The E2F family of transcription factors plays an important role in the control of the cell cycle, cell proliferation, and differentiation, and their role in ovarian function is just emerging. Although some evidence suggests a possible role of E2F1 in ovarian follicular development, what regulates its production in ovarian cells is unknown. Objectives of this study were to determine: 1) if E2F1 gene expression in granulosa cells (GC) and theca cells (TC) change with follicular development, and 2) if E2F1 mRNA abundance in TC and GC is hormonally regulated. Using real-time PCR, E2F1 mRNA abundance in GC was 5.5-fold greater (P < 0.05) in small (1-5 mm) than large (>8 mm) follicles, but in TC, E2F1 expression did not differ among follicle sizes. Small-follicle GC had 2.1-fold greater (P < 0.05) E2F1 mRNA than TC. In small-follicle GC, FGF9 induced a 7.6-fold increase in E2F1 mRNA abundance, however, FGF9 did not affect (P > 0.10) abundance of E2F1 mRNA in large-follicle TC or GC. Follicle-stimulating hormone (FSH) had no effect (P > 0.10) on E2F1 gene expression in small- or large-follicle GC. Small-follicle GC were concomitantly treated with insulin-like growth factor 1 (IGF1; 30 ng/mL), FSH (30 ng/mL), and either 0 or 30 ng/mL of FGF9 with or without 50 µM of an E2F inhibitor (E2Fi; HLM0064741); FGF9 alone increased (P < 0.05) GC numbers, whereas E2Fi alone decreased (P < 0.05) GC numbers, and concomitant treatment of E2Fi with FGF9 blocked (P < 0.05) this stimulatory effect of FGF9. Estradiol production was inhibited (P < 0.05) by FGF9 alone and concomitant treatment of E2Fi with FGF9 attenuated (P < 0.05) this inhibitory effect of FGF9. Small-follicle GC treated with E2Fi decreased (P < 0.05) E2F1 mRNA abundance by 70%. Collectively, our studies show that GC E2F1 mRNA is developmentally and hormonally regulated in cattle. Inhibition of E2F1 reduced FGF9-induced GC proliferation and attenuated FGF9-inhibited estradiol production, indicating that E2F1 may be involved in follicular development in cattle.//////////////////
Expression regulated by
mir17
Comment
miR-17-5p affects porcine granulosa cell growth and estradiol synthesis by targeting E2F1 gene. Zhang S et al. (2019) Female fertility potential is based on the development and growth of ovarian follicles. Our previous study showed that miR-17-5p was significantly differently expressed in pre-ovulatory ovarian follicles of Large White (LW) and Chinese Taihu (CT) sows. In the present study, we investigated the role of miR-17-5p in ovarian follicle development. We demonstrated that miR-17-5p overexpression significantly decreased the luciferase reporter activity containing the E2F transcription factor 1 (E2F1) 3'untranslated region (3'UTR), suppressed the E2F1 expression, whereas the miR-17-5p inhibition increased the E2F1 expression in porcine granulosa cells (pGCs). Meanwhile, miR-17-5p overexpression or E2F1 knockdown promoted cell growth, follicular development marker genes (LHR, CYP19A1 and AREG) expression and estradiol synthesis, and miR-17-5p inhibition suppressed cell growth, follicular development marker genes (LHR, CYP19A1 and AREG) expression and estradiol synthesis in pGCs. Furthermore, E2F1 knockdown increased CYP19A1 promoter activity. This study suggests that miR-17-5p regulates pGC growth and estradiol synthesis by targeting E2F1 gene. This article is protected by copyright. All rights reserved.//////////////////
Transactivation of miR-320 by miR-383 regulates granulosa cell functions by targeting E2F1 and SF-1* Yin M 2014 et al.
Our previous studies have shown that miR-320 is one of the most down-regulated miRNAs in mouse ovarian granulosa cells (GCs) after TGF-1 treatment. However, the underlying mechanisms of miR-320 involved in GC function during follicular development remain unknown. In this study, we found that PMSG treatment resulted in the suppression of miR-320 expression in a time-dependent manner. miR-320 was mainly expressed in GCs and oocytes of mouse ovarian follicles in follicular development. Overexpression of miR-320 inhibited estradiol (E2) synthesis and proliferation of GCs through targeting E2F1 and SF-1. E2F1/SF-1 mediated miR-320-induced suppression of GC proliferation and of GC steroidogenesis. FSH down-regulated the expression of miR-320 and regulated the function of miR-320 in mouse GCs. miR-383 promoted the expression of miR-320 and enhanced miR-320-mediated suppression of GC proliferation. Injection of miR-320 into the ovaries of mice partially promoted the production of testosterone and progesterone, but inhibited E2 release in vivo. Moreover, the expression of miR-320 and miR-383 was up-regulated in the follicular fluid of polycystic ovarian syndrome (PCOS) patients, while the expression of E2F1 and SF-1 was down-regulated in GCs. These data demonstrated that miR-320 regulates the proliferation and steroid production by targeting E2F1 and SF-1 in the follicular development. Understanding the regulation of miRNA biogenesis and function in the follicular development will potentiate the usefulness of miRNA in the treatment of reproduction and some steroid-related disorders.
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