Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes Beverdam A, et al.This gene was upregulated in 11.5 dpc female somatic gonad cells.
NCBI Summary:
This gene is thought to regulate cell cycle progression. It is induced by p53 in response to DNA damage, or by sublytic levels of complement system proteins that result in activation of the cell cycle. The encoded protein localizes to the cytoplasm during interphase and to centrosomes during mitosis. The protein forms a complex with polo-like kinase 1. The protein also translocates to the nucleus in response to treatment with complement system proteins, and can associate with and increase the kinase activity of cell division cycle 2 protein. In different assays and cell types, overexpression of this protein has been shown to activate or suppress cell cycle progression. [provided by RefSeq, Jul 2008]
General function
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Cellular localization
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Ovarian function
Ovulation, Luteinization
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Expression regulated by
LH
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Response Gene to Complement 32 (Rgc32) expression is induced by the LH surge and regulated by LH-induced mediators in the rodent ovary. Park ES et al. Rgc32 has recently been suggested to be expressed in the ovary and regulated by RUNX1, a transcription factor, induced in periovulatory follicles. In the present study, we determined the expression profile of Rgc32 gene in the rodent ovary throughout the reproductive cycle and the regulatory mechanism(s) involved in Rgc32 expression during the periovulatory period. Northern blot and in situ hybridization analyses revealed the up-regulation of Rgc32 expression in periovulatory follicles. Rgc32 mRNA was also localized to newly forming corpora lutea (CL) and CL from previous estrous cycles. Further studies using hormonally-induced luteal and luteolysis models revealed a transient increase in levels of Rgc32 mRNA at the time of functional regression of the CL. Next, the regulation of Rgc32 expression was investigated in vitro using rat preovulatory granulosa cells. The effect of hCG on Rgc32 expression was mimicked by forskolin, but not PMA, and was mediated by the activation of progesterone receptors and the EGF-signaling pathway. The mechanism by which RUNX1 regulates Rgc32 expression was investigated using ChIP and Rgc32 promoter-luciferase reporter assays. Data from these assays revealed direct binding of RUNX1 in the Rgc32 promoter region in vivo as well as the involvement of RUNX binding sites in the transactivation of the Rgc32 promoter in vitro. In summary, the present study demonstrated the spatial/temporal-specific expression of Rgc32 in the ovary and provided evidence of LH-initiated and RUNX1-mediated expression of Rgc32 gene in luteinizing granulosa cells.
Ovarian localization
Primordial Germ Cell, Granulosa, Luteal cells
Comment
RUNX2 Transcription Factor Regulates Gene Expression in Luteinizing Granulosa Cells of Rat Ovaries. Park ES et al. The LH surge promotes terminal differentiation of follicular cells to become luteal cells. RUNX2 has been shown to play an important role in cell differentiation, but the regulation of Runx2 expression and its function in the ovary remain to be determined. The present study examined 1) the expression profile of Runx2 and its partner CBFbeta during the periovulatory period, 2) regulatory mechanisms of Runx2 expression, and 3) its potential function in the ovary. Runx2 expression was induced in periovulatory granulosa cells of human and rodent ovaries. RUNX2 and core binding factor-beta (CBFbeta) proteins in nuclear extracts and RUNX2 binding to a consensus binding sequence increased after human chorionic gonadotropin (hCG) administration. This in vivo up-regulation of Runx2 expression was recapitulated in vitro in preovulatory granulosa cells by stimulation with hCG. The hCG-induced Runx2 expression was reduced by antiprogestin (RU486) and EGF-receptor tyrosine kinase inhibitor (AG1478), indicating the involvement of EGF-signaling and progesterone-mediated pathways. We also found that in the C/EBPbeta knockout mouse ovary, Runx2 expression was reduced, indicating C/EBPbeta-mediated expression. Next, the function of RUNX2 was investigated by suppressing Runx2 expression by small interfering RNA in vitro. Runx2 knockdown resulted in reduced levels of mRNA for Rgc32, Ptgds, Fabp6, Mmp13, and Abcb1a genes. Chromatin immunoprecipitation analysis demonstrated the binding of RUNX2 in the promoter region of these genes, suggesting that these genes are direct downstream targets of RUNX2. Collectively, the present data indicate that the LH surge-induced RUNX2 is involved in various aspects of luteal function by directly regulating the expression of diverse luteal genes.