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排卵信号通过差异染色质可及性引发 LRH-1 转录开关。

The Ovulatory Signal Precipitates LRH-1 Transcriptional Switching Mediated by Differential Chromatin Accessibility.

机构信息

Département de biologie, Faculté des sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.

Centre de recherche en reproduction et fertilité, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, Canada.

出版信息

Cell Rep. 2019 Aug 27;28(9):2443-2454.e4. doi: 10.1016/j.celrep.2019.07.088.

DOI:10.1016/j.celrep.2019.07.088
PMID:31461657
Abstract

In the ovary, follicular growth and maturation are complicated processes that involve a series of morphological and physiological changes in oocytes and somatic cells leading to ovulation and luteinization, essential processes for fertility. Given the complexity of ovulation, characterization of genome-wide regulatory elements is essential to understand the mechanisms governing the expression of specific genes in the rapidly differentiating follicle. We therefore employed a systems biology approach to determine global transcriptional mechanisms during the early stages of the ovulatory process. We demonstrate that, following the hormonal signal that initiates ovulation, granulosa cells undergo major modification of distal regulatory elements, which coincides with cistrome reprogramming of the indispensable orphan nuclear receptor liver receptor homolog-1 (LRH-1). This cistromic reorganization correlates with the extensive changes in gene expression in granulosa cells leading to ovulation. Together, our study yields a highly detailed transcriptional map delineating ovarian cell differentiation during the initiation of ovulation.

摘要

在卵巢中,卵泡的生长和成熟是一个复杂的过程,涉及卵母细胞和体细胞的一系列形态和生理变化,导致排卵和黄体化,这是生育所必需的过程。鉴于排卵的复杂性,对全基因组调控元件的特征进行描述对于理解在快速分化的卵泡中特定基因表达的机制至关重要。因此,我们采用系统生物学的方法来确定排卵过程早期的全局转录机制。我们证明,在启动排卵的激素信号之后,颗粒细胞经历了远端调控元件的重大修饰,这与必需的孤儿核受体肝受体同源物-1(LRH-1)顺式作用元件的重新编程同时发生。这种顺式元件的重组与导致排卵的颗粒细胞中基因表达的广泛变化相关。总之,我们的研究提供了一个高度详细的转录图谱,描绘了排卵启动过程中卵巢细胞的分化。

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