Follistatin treatment modifies DNA methylation of theCDX2gene in bovine preimplantation embryos

文献类型： 外文期刊

第一作者： Ashry, Mohamed

作者： Ashry, Mohamed;Rajput, Sandeep K.;Folger, Joseph K.;Smith, George W.;Ashry, Mohamed;Knott, Jason G.;Ashry, Mohamed;Rajput, Sandeep K.;Yang, Chunyan

作者机构：

关键词： bovine preimplantation embryo; CDX2; DNA methylation; follistatin

期刊名称：MOLECULAR REPRODUCTION AND DEVELOPMENT （ 影响因子：2.609； 五年影响因子：3.47 ）

ISSN： 1040-452X

年卷期： 2020 年 87 卷 9 期

页码：

收录情况： SCI

摘要： CDX2 plays a crucial role in the formation and maintenance of the trophectoderm epithelium in preimplantation embryos. Follistatin supplementation during the first 72 hr of in vitro culture triggers a significant increase in blastocyst rates,CDX2expression, and trophectoderm cell numbers. However, the underlying epigenetic mechanisms by which follistatin upregulatesCDX2expression are not known. Here, we investigated whether stimulatory effects of follistatin are linked to alterations in DNA methylation within key regulatory regions of theCDX2gene. In vitro-fertilized (IVF) zygotes were cultured with or without 10 ng/ml of recombinant human follistatin for 72 hr, then cultured without follistatin until Day 7. The bisulfite-sequencing analysis revealed differential methylation (DM) at specific CpG sites within theCDX2promoter and intron 1 following follistatin treatment. These DM CpG sites include five hypomethylated sites at positions -1384, -1283, -297, -163, and -23, and four hypermethylated sites at positions -1501, -250, -243, and +20 in the promoter region. There were five hypomethylated sites at positions +3060, +3105, +3219, +3270, and +3545 in intron 1. Analysis of transcription factor binding sites using MatInspector combined with a literature search revealed a potential association between differentially methylated CpG sites and putative binding sites for key transcription factors involved in regulatingCDX2expression. The hypomethylated sites are putative binding sites for FXR, STAF, OCT1, KLF, AP2 family, and P53 protein, whereas the hypermethylated sites are putative binding sites for NRSF. Collectively, our results suggest that follistatin may increaseCDX2expression in early bovine embryos, at least in part, by modulating DNA methylation at key regulatory regions.

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