Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development.,Molecular Reproduction and Development

当前位置： X-MOL 学术 › Mol. Reprod. Dev. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development.
Molecular Reproduction and Development ( IF 2.7 ) Pub Date : 2020-03-25 , DOI: 10.1002/mrd.23339
Qian Zhou _{1,

2} , Qing-Ren Meng ₃ , Tie-Gang Meng ₁ , Qi-Long He ₄ , Zheng-Hui Zhao _{1,

2} , Qian-Nan Li ₁ , Wen-Long Lei _{1,

2} , Shu-Zhen Liu ₄ , Heide Schatten ₅ , Zhen-Bo Wang _{1,

2} , Qing-Yuan Sun _{1,

2}

Affiliation

BRG1‐associated factor 250a (BAF250a) is a component of the SWI/SNF adenosine triphosphate‐dependent chromatin remodeling complex, which has been shown to control chromatin structure and transcription. BAF250a was reported to be a key component of the gene regulatory machinery in embryonic stem cells controlling self‐renewal, differentiation, and cell lineage decisions. Here we constructed Baf250a ^F/F;Gdf9‐cre (Baf250a ^CKO) mice to specifically delete BAF250a in oocytes to investigate the role of maternal BAF250a in female germ cells and embryo development. Our results showed that BAF250a deletion did not affect folliculogenesis, ovulation, and fertilization, but it caused late embryonic death. RNA sequencing analysis showed that the expression of genes involved in cell proliferation and differentiation, tissue morphogenesis, histone modification, and nucleosome remodeling were perturbed in Baf250a ^CKO MII oocytes. We showed that covalent histone modifications such as H3K27me3 and H3K27ac were also significantly affected in oocytes, which may reduce oocyte quality and lead to birth defects. In addition, the DNA methylation level of Igf2r, Snrpn , and Peg3 differentially methylated regions was decreased in Baf250a ^CKO oocytes. Quantitative real‐time polymerase chain reaction analysis showed that the relative messenger RNA (mRNA) expression levels of Igf2r and Snrpn were significantly increased. The mRNA expression level of Dnmt1, Dnmt3a, Dnmt3l , and Uhrf1 was decreased, and the protein expression in these genes was also reduced, which might be the cause for impaired imprinting establishment. In conclusion, our results demonstrate that BAF250a plays an important role in oocyte transcription regulation, epigenetic modifications, and embryo development.

中文翻译：

BAF250a的缺失影响卵母细胞表观遗传修饰和胚胎发育。

BRG1相关因子250a（BAF250a）是SWI / SNF依赖于三磷酸腺苷的染色质重塑复合物的一个组成部分，已显示它可控制染色质的结构和转录。据报道，BAF250a是胚胎干细胞中控制自我更新，分化和细胞谱系决定的基因调控机制的关键组成部分。在这里，我们构建了Baf250a ^{F / F}；Gdf9-cre（Baf250a ^CKO）小鼠，通过特异性删除卵母细胞中的BAF250a来研究母体BAF250a在雌性生殖细胞和胚胎发育中的作用。我们的结果表明，BAF250a缺失不会影响卵泡的形成，排卵和受精，但会导致晚期胚胎死亡。RNA测序分析表明，与细胞增殖和分化，组织形态发生，组蛋白修饰和核小体重塑有关的基因的表达在Baf250a ^CKO MII卵母细胞中受到干扰。我们发现卵母细胞中的共价组蛋白修饰如H3K27me3和H3K27ac也受到显着影响，这可能降低卵母细胞质量并导致先天缺陷。此外，Igf2r，Snrpn和Peg3的DNA甲基化水平Baf250a ^CKO卵母细胞差异甲基化区域减少。实时定量聚合酶链反应分析显示，Igf2r和Snrpn的相对信使RNA（mRNA）表达水平显着提高。Dnmt1，Dnmt3a，Dnmt3l和Uhrf1的mRNA表达水平降低，并且这些基因中的蛋白质表达也降低，这可能是印迹建立受损的原因。总之，我们的结果证明BAF250a在卵母细胞转录调节，表观遗传修饰和胚胎发育中起着重要作用。

更新日期：2020-03-25

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11