1. Analysis of active chromatin modifications in early mammalian embryos reveals uncoupling of H2A.Z acetylation and H3K36 trimethylation from embryonic genome activation
- Author
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Céline Ziegler-Birling, Ana Bošković, Ambre Bender, Laurence Gall, Maria-Elena Torres-Padilla, Nathalie Beaujean, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), U964, Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), ANR-09-Blanc-0114, EpiGeneSys NoE, ERCStg 'NuclearPotency' and the FP7 Marie-Curie Actions ITN Nucleosome4D, REVIVE consortium (ANR 'Laboratoire d'Excellence' program), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie du développement et reproduction (BDR), and Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)
- Subjects
Transcriptional Activation ,Cancer Research ,Euchromatin ,Embryonic Development ,Biology ,Methylation ,Chromatin remodeling ,Epigenesis, Genetic ,Histones ,Mice ,Histone H1 ,Histone H2A ,Animals ,Nucleosome ,Histone code ,histone variants ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Molecular Biology ,histone modifications ,Gene Expression Regulation, Developmental ,Acetylation ,[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,Embryo, Mammalian ,Molecular biology ,Chromatin ,Blastocyst ,Histone methyltransferase ,mammalian embryo ,embryonic structures ,Cattle ,epigenetic - Abstract
Early embryonic development is characterized by dramatic changes in cell potency and chromatin organization. The role of histone variants in the context of chromatin remodeling during embryogenesis remains under investigated. In particular, the nuclear distribution of the histone variant H2A.Z and its modifications have not been examined. Here we investigated the dynamics of acetylation of H2A.Z and two other active chromatin marks, H3K9ac and H3K36me3, throughout murine and bovine pre-implantation development. We show that H2A.Z distribution is dynamic during the earliest stages of mouse development, with protein levels significantly varying across stages and lowest at the 2-cell stage. When present, H2A.Z localizes preferentially to euchromatin at all stages analyzed. H2A.Z is acetylated in pre-implantation blastomeres and is preferentially localized to euchromatin, in line with the known role of H2A.Zac in transcriptional activation. Interestingly, however, H2A.Zac is undetectable in mouse embryos at the 2-cell stage, the time of major embryonic genome activation (EGA). Similarly, H3K36me3 is present exclusively in the maternal chromatin immediately after fertilization but becomes undetectable in interphase nuclei at the 2-cell stage, suggesting uncoupling of these active marks with global embryonic transcription activation. In bovine embryos, which undergo EGA at the 8-cell stage, H2A.Zac can be detected in zygotes, 4-, 8- and 16-cell stage embryos as well as in blastocysts, indicating that the dynamics of H2A.Zac is not conserved in mammals. In contrast, H3K36me3 displays mostly undetectable and heterogeneous localization pattern throughout bovine pre-implantation development. Thus, our results suggest that 'canonical' active chromatin marks exhibit a dynamic behavior in embryonic nuclei, which is both stage- and species-specific. We hypothesize that chromatin of early embryonic nuclei is subject to fine-tuning through differential acquisition of histone marks, allowing for proper chromatin remodeling and developmental progression in a species-specific fashion.
- Published
- 2012
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