title: 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.
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction - BioRep, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Werner G
authors.initials: WG
authors.lastname: Glanzner
authors.affiliation: Department of Animal Science, McGill University, Sainte Anne de Bellevue, Quebec, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Wachter
authors.affiliation: Department of Animal Science, McGill University, Sainte Anne de Bellevue, Quebec, Canada.
authors.forename: Ana Rita S
authors.initials: AR
authors.lastname: Coutinho
authors.affiliation: Department of Animal Science, McGill University, Sainte Anne de Bellevue, Quebec, Canada.
authors.forename: Marcelo S
authors.initials: MS
authors.lastname: Albornoz
authors.affiliation: Department of Animal Science, McGill University, Sainte Anne de Bellevue, Quebec, Canada.
authors.forename: Raj
authors.initials: R
authors.lastname: Duggavathi
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction - BioRep, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Paulo B D
authors.initials: PB
authors.lastname: GonÇAlves
authors.affiliation: Department of Animal Science, McGill University, Sainte Anne de Bellevue, Quebec, Canada.
authors.forename: Vilceu
authors.initials: V
authors.lastname: Bordignon
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D004265:DNA Helicases / Q000096:biosynthesis*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D056466:Histone Demethylases / Q000096:biosynthesis*; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D013552:Swine
chemical_list: D006657:Histones; D056466:Histone Demethylases; D004265:DNA Helicases