Core Binding Factor-β Knockdown Alters Ovarian Gene Expression and Function in the Mouse
| Autor: | Misung Jo, Ichiro Taniuchi, Birendra Mishra, Thomas E. Curry, Ji Yeon Park, Jan A. Gossen, Kalin Wilson |
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| Rok vydání: | 2016 |
| Předmět: |
Ovulation
0301 basic medicine endocrine system Core Binding Factor beta Subunit Granulosa cell Transcription factor complex Core Binding Factor Alpha 1 Subunit Protein Serine-Threonine Kinases Biology Core binding factor Chorionic Gonadotropin Immediate-Early Proteins Mice 03 medical and health sciences chemistry.chemical_compound Endocrinology Ovarian Follicle Corpus Luteum Wnt4 Protein Proto-Oncogene Proteins Gene expression Animals Molecular Biology Transcription factor Original Research Mice Knockout Gene knockdown Granulosa Cells Ovary Core Binding Factor alpha Subunits General Medicine Molecular biology Cell biology Luteinization 030104 developmental biology Gene Expression Regulation RUNX1 chemistry Core Binding Factor Alpha 2 Subunit Female |
| Zdroj: | Molecular Endocrinology. 30:733-747 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Core binding factor (CBF) is a heterodimeric transcription factor complex composed of a DNA-binding subunit, one of three runt-related transcription factor (RUNX) factors, and a non-DNA binding subunit, CBFβ. CBFβ is critical for DNA binding and stability of the CBF transcription factor complex. In the ovary, the LH surge increases the expression of Runx1 and Runx2 in periovulatory follicles, implicating a role for CBFs in the periovulatory process. The present study investigated the functional significance of CBFs (RUNX1/CBFβ and RUNX2/CBFβ) in the ovary by examining the ovarian phenotype of granulosa cell-specific CBFβ knockdown mice; CBFβ f/f * Cyp19 cre. The mutant female mice exhibited significant reductions in fertility, with smaller litter sizes, decreased progesterone during gestation, and fewer cumulus oocyte complexes collected after an induced superovulation. RNA sequencing and transcriptome assembly revealed altered expression of more than 200 mRNA transcripts in the granulosa cells of Cbfb knockdown mice after human chorionic gonadotropin stimulation in vitro. Among the affected transcripts are known regulators of ovulation and luteinization including Sfrp4, Sgk1, Lhcgr, Prlr, Wnt4, and Edn2 as well as many genes not yet characterized in the ovary. Cbfβ knockdown mice also exhibited decreased expression of key genes within the corpora lutea and morphological changes in the ovarian structure, including the presence of large antral follicles well into the luteal phase. Overall, these data suggest a role for CBFs as significant regulators of gene expression, ovulatory processes, and luteal development in the ovary. |
| Databáze: | OpenAIRE |
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