He Hui, Kong Shuangbo, Liu Fei, Zhang Shuang, Jiang Yaling, Liao Yixin, Jiang Yufei, Li Qian, Wang Bingyan, Zhou Zuomin, Wang Haibin, Huo Ran
State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China.
Biol Reprod. 2015 Jul;93(1):13. doi: 10.1095/biolreprod.115.129015. Epub 2015 Jun 3.
Uterine stromal cells undergo extensive proliferation and differentiation during postimplantation development, a process known as decidualization. While a range of signaling molecules have been demonstrated to play essential roles in this event, its potential epigenetic regulatory mechanisms remain largely unknown. Retinoblastoma binding protein 7 (Rbbp7) is a protein reported as a core component of many histone modification and chromatin remodeling complexes. In the present study, our in situ hybridization and immunochemistry analysis first reveals a spatiotemporal expression of Rbbp7 in the uterus during the peri-implantation period. Observations of remarkable induction of Rbbp7 expression in uterine stromal cells in response to progesterone-nuclear receptor PR signaling point to its potential physiological significance during postimplantation uterine development. Employing a stealth RNA knockdown approach, combined with primary murine uterine stromal cell culture and an in vitro-induced decidualization model, we further demonstrate that Rbbp7 silencing compromises stromal cell decidualization via attenuating histone H4 acetylation and cyclin D3 expression. The results collectively suggest that Rbbp7 is a potentially functional player regulating normal histone acetylation modification and cyclin D3 expression in stromal cells during postimplantation decidual development.
在植入后发育过程中,子宫基质细胞会经历广泛的增殖和分化,这一过程被称为蜕膜化。虽然一系列信号分子已被证明在这一过程中发挥重要作用,但其潜在的表观遗传调控机制仍 largely 未知。视网膜母细胞瘤结合蛋白 7(Rbbp7)是一种被报道为许多组蛋白修饰和染色质重塑复合物核心成分的蛋白质。在本研究中,我们的原位杂交和免疫化学分析首次揭示了 Rbbp7 在围着床期子宫中的时空表达。观察到子宫基质细胞中 Rbbp7 表达因孕酮核受体 PR 信号而显著诱导,这表明其在植入后子宫发育过程中的潜在生理意义。采用 stealth RNA 敲低方法,结合原代小鼠子宫基质细胞培养和体外诱导蜕膜化模型,我们进一步证明 Rbbp7 沉默通过减弱组蛋白 H4 乙酰化和细胞周期蛋白 D3 表达而损害基质细胞蜕膜化。这些结果共同表明,Rbbp7 是植入后蜕膜发育过程中调节基质细胞正常组蛋白乙酰化修饰和细胞周期蛋白 D3 表达的潜在功能性参与者。