Altered expression of BRG1 and histone demethylases, and aberrant H3K4 methylation in less developmentally competent embryos at the time of embryonic genome activation

Abstract

Epigenetics is a fundamental regulator underlying many biological functions, such as development and cell differentiation. Epigenetic modifications affect key chromatin regulation, including transcription and DNA repair, which are critical for normal embryo development. In this study, we profiled the expression of epigenetic modifiers and patterns of epigenetic changes in porcine embryos around the period of embryonic genome activation (EGA). We observed that Brahma-related gene 1 (BRG1) and Lysine demethylase 1A (KDM1A), which can alter the methylation status of lysine 4 in histone 3 (H3K4), localize to the nucleus at Day 3-4 of development. We then compared the abundance of epigenetic modifiers between early- and late-cleaving embryos, which were classified based on the time to the first cell cleavage, to investigate if their nuclear localization contributes to developmental competence. The mRNA abundance of BRG1, KDM1A, as well as other lysine demethylases (KDM1B, KDM5A, KDM5B, and KDM5C), were significantly higher in late- compared to early-cleaving embryos near the EGA period, although these difference disappeared at the blastocyst stage. The abundance of H3K4 mono- (H3K4me) and di-methylation (H3K4me2) during the EGA period was reduced in late-cleaving and less developmentally competent embryos. By contrast, BRG1, KDM1A, and H3K4me2 abundance was greater in embryos with more than eight cells at Day 3-4 of development compared to those with fewer than four cells. These findings suggest that altered epigenetic modifications of H3K4 around the EGA period may affect the developmental capacity of porcine embryos to reach the blastocyst stage. Mol. Reprod. Dev. 84: 19-29, 2017. © 2016 Wiley Periodicals, Inc.

Whole-Genome Methylation Analysis Reveals Epigenetic Variation in Cloned and Donor Pigs

“…Between the CP and DP Under the same feeding regime and environmental conditions, the first calving age of the CP was 51 days older than the DP, and the litter size of the CP was four piglets less and two live piglets less than the DP in the first two parities and in the first three parities, respectively ( Table 3). DNA methylation was a common epigenetic modification and affected oocyte meiotic maturation and embryonic development, which in turn affecting the litter size Glanzner et al, 2017;Hwang et al, 2017a;. In this study, we found that the level of methylation and the methylated functional regions of the same tissue between the two pigs were different.…”

Dynamic Methylation Changes of DNA and H3K4 by RG108 Improve Epigenetic Reprogramming of Somatic Cell Nuclear Transfer Embryos in Pigs

“…It has been reported that many different epigenetic modifications can change the structure of chromatin and participate in the regulation of gene expression and nuclear reprogramming during SCNT [26,27]. However, there is no clear consensus about how the DNA methylation pattern linked to the histone modifications and how the complex epigenetic information is integrated and translated into defined chromatin structures and gene expression level.…”

The histone lysine demethylase KDM7A is required for normal development and first cell lineage specification in porcine embryos

“…Histone lysine methyltransferases (KMTs) and KDMs enzymes regulate gene expression by modulating histone methylation levels [17]. Among all the histone modifications, the methylation levels of lysines 4, 9 and 27 in histone 3 are the most studied and have been shown to regulate embryo development and EGA transition [18][19][20][21][22][23], as well as cell differentiation and reprogramming [24][25][26][27][28]. Moreover, functional studies revealed that active removal of epigenetic marks is crucial for embryo development.…”