histone h3 lysine 27 methylation asymmetry on developmentally-regulated promoters distinguish the first two lineages in mouse preimplantation embryos27组蛋白h3赖氨酸甲基化不对称developmentally-regulated推动者区分前两个血统在老鼠胚胎植入前的胚胎.pdfVIP

Histone H3 Lysine 27 Methylation Asymmetry on Developmentally-Regulated Promoters Distinguish the First Two Lineages in Mouse Preimplantation Embryos 1¤ 1 2 3 1 John Arne Dahl , Andrew H. Reiner , Arne Klungland , Teruhiko Wakayama , Philippe Collas * 1 Institute of Basic Medical Sciences, University of Oslo and Norwegian Center for Stem Cell Research, Oslo, Norway, 2 Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway, 3 Center for Developmental Biology, RIKEN, Chuo-ku, Kobe, Japan Abstract First lineage specification in the mammalian embryo leads to formation of the inner cell mass (ICM) and trophectoderm (TE), which respectively give rise to embryonic and extraembryonic tissues. We show here that this first differentiation event is accompanied by asymmetric distribution of trimethylated histone H3 lysine 27 (H3K27me3) on promoters of signaling and developmentally-regulated genes in the mouse ICM and TE. A genome-wide survey of promoter occupancy by H3K4me3 and H3K27me3 indicates that both compartments harbor promoters enriched in either modification, and promoters co- enriched in trimethylated H3K4 and H3K27 linked to developmental and signaling functions. The majority of H3K4/K27me3 co-enriched promoters are distinct between the two lineages, primarily due to differences in the distribution of H3K27me3. Derivation of embryonic stem cells leads to significant losses and gains of H3K4/K27me3 co-enriched promoters relative to the ICM, with distinct contributions of (de)methylation events on K4 and K27. Our results show histone trimethylation asymmetry on promoters in the first two developmental lineages, and highlight a