核心结合因子-β敲低改变小鼠卵巢基因表达和功能。

Q Biochemistry, Genetics and Molecular Biology
Molecular endocrinology Pub Date : 2016-07-01 Epub Date: 2016-05-13 DOI:10.1210/me.2015-1312
Kalin Wilson, Jiyeon Park, Thomas E Curry, Birendra Mishra, Jan Gossen, Ichiro Taniuchi, Misung Jo
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引用次数: 12

摘要

核心结合因子(CBF)是一种异二聚体转录因子复合物,由dna结合亚基、三个矮子相关转录因子(RUNX)因子之一和非dna结合亚基CBFβ组成。CBFβ对DNA结合和CBF转录因子复合物的稳定性至关重要。在卵巢中,黄体生成素激增增加了卵泡中Runx1和Runx2的表达,暗示CBFs在排卵过程中起作用。本研究通过检测颗粒细胞特异性CBFβ敲除小鼠卵巢表型,探讨了卵巢中CBFs (RUNX1/CBFβ和RUNX2/CBFβ)的功能意义;CBFβ f/f * Cyp19 cre。突变雌性小鼠的生育能力明显下降,产仔数减少,妊娠期间孕激素下降,诱导超排卵后收集的卵母细胞复合物减少。RNA测序和转录组组装显示,体外人绒毛膜促性腺激素刺激后,Cbfb敲低小鼠颗粒细胞中200多种mRNA转录物的表达发生改变。受影响的转录本包括已知的排卵和黄体生成调节因子,包括strp4、Sgk1、Lhcgr、Prlr、Wnt4和Edn2,以及许多尚未在卵巢中发现的基因。Cbfβ敲除小鼠还表现出黄体内关键基因的表达减少和卵巢结构的形态学变化,包括黄体期存在大的窦卵泡。总的来说,这些数据表明CBFs在卵巢中作为基因表达、排卵过程和黄体发育的重要调节因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Core Binding Factor-β Knockdown Alters Ovarian Gene Expression and Function in the Mouse.

Core Binding Factor-β Knockdown Alters Ovarian Gene Expression and Function in the Mouse.

Core Binding Factor-β Knockdown Alters Ovarian Gene Expression and Function in the Mouse.

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.

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来源期刊
Molecular endocrinology
Molecular endocrinology 医学-内分泌学与代谢
CiteScore
3.49
自引率
0.00%
发文量
0
审稿时长
12 months
期刊介绍: Molecular Endocrinology provides a forum for papers devoted to describing molecular mechanisms by which hormones and related compounds regulate function. It has quickly achieved a reputation as a high visibility journal with very rapid communication of cutting edge science: the average turnaround time is 28 days from manuscript receipt to first decision, and accepted manuscripts are published online within a week through Rapid Electronic Publication. In the 2008 Journal Citation Report, Molecular Endocrinology is ranked 16th out of 93 journals in the Endocrinology and Metabolism category, with an Impact Factor of 5.389.
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