한빛사 논문
Abstract
John Arne Dahl1*, Inkyung Jung2*, Havard Aanes1, Gareth D. Greggains3, Adeel Manaf1, Mads Lerdrup4, Guoqiang Li2, Samantha Kuan2, Bin Li2, Ah Young Lee2, Sebastian Preissl2, Ingunn Jermstad5, Mads Haugland Haugen6, Rajikala Suganthan1, Magnar Bjøras1,7, Klaus Hansen4, Knut Tomas Dalen5,8, Peter Fedorcsak3, Bing Ren2,9,10 & Arne Klungland1,11
1Department of Microbiology, Oslo University Hospital, Rikshospitalet, NO-0027 Oslo, Norway. 2Ludwig Institute for Cancer Research, La Jolla, California 92093, USA. 3Department of Gynecology, Section for Reproductive Medicine, Oslo University Hospital, Rikshospitalet, NO-0027, Oslo, Norway. 4The Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, DK-2200 Copenhagen, Denmark. 5Norwegian Transgenic Centre, Institute of Basic Medical Sciences, University of Oslo, NO-0317 Oslo, Norway. 6Department of Tumor Biology and Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, NO-0424 Oslo, Norway. 7Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway. 8Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, NO-0027 Oslo, Norway. 9Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, California 92093, USA. 10UCSD Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA. 11Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, NO-0317 Oslo, Norway.
*These authors contributed equally to this work.
Correspondence to : John Arne Dahl or Bing Ren or Arne Klungland
Maternal-to-zygotic transition (MZT) is essential for the formation of a new individual, but is still poorly understood despite recent progress in analysis of gene expression and DNA methylation in early embryogenesis1, 2, 3, 4, 5, 6, 7, 8, 9. Dynamic histone modifications may have important roles in MZT10, 11, 12, 13, but direct measurements of chromatin states have been hindered by technical difficulties in profiling histone modifications from small quantities of cells. Recent improvements allow for 500 cell-equivalents of chromatin per reaction, but require 10,000 cells for initial steps14 or require a highly specialized microfluidics device that is not readily available15. We developed a micro-scale chromatin immunoprecipitation and sequencing (μChIP?seq) method, which we used to profile genome-wide histone H3 lysine methylation (H3K4me3) and acetylation (H3K27ac) in mouse immature and metaphase II oocytes and in 2-cell and 8-cell embryos. Notably, we show that ~22% of the oocyte genome is associated with broad H3K4me3 domains that are anti-correlated with DNA methylation. The H3K4me3 signal becomes confined to transcriptional-start-site regions in 2-cell embryos, concomitant with the onset of major zygotic genome activation. Active removal of broad H3K4me3 domains by the lysine demethylases KDM5A and KDM5B is required for normal zygotic genome activation and is essential for early embryo development. Our results provide insight into the onset of the developmental program in mouse embryos and demonstrate a role for broad H3K4me3 domains in MZT.
논문정보
관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기