Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development. Issue 5 (25th March 2020)

• Record Type: Journal Article
• Authors: Zhou, Qian; Meng, Qing‐Ren; Meng, Tie‐Gang; He, Qi‐Long; Zhao, Zheng‐Hui; Li, Qian‐Nan; Lei, Wen‐Long; Liu, Shu‐Zhen; Schatten, Heide; Wang, Zhen‐Bo; Sun, Qing‐Yuan
• Is Part Of: Molecular reproduction and development. Volume 87:Issue 5(2020)
• Page Start: 550
• Page End: 564
• Publication Date: 2020-03-25
• Subjects: BAF250a -- epigenetic modification -- oocyte maturation -- SWI/SNF complex; Reproduction -- Periodicals; Molecular biology -- Periodicals; Molecular genetics -- Periodicals; Embryology -- Periodicals; 571.8
• DOI: 10.1002/mrd.23339
• Languages: English
• ISSNs: 1040-452X

Abstract

Abstract: 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. Abstract : Our findings of epigenetic changes in maternal BRG1‐associated factor 250a (BAF250a) deleted oocytes suggest that BAF250a mutation influences the correct establishment of maternal imprinting genes and histone modifications in oocytes, which are critical for oocyte epigenetic maturation. This is the first time to show that the loss of BAF250a results in epigenetic abnormalities in oocytes.