Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition
Three papers in this issue of Nature use highly sensitive ChIP–seq assays to describe the dynamic patterns of histone modifications during early mouse embryogenesis, showing that oocytes have a distinctive epigenome and providing insights into how the maternal gene expression program transitions to...
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Published in | Nature (London) Vol. 537; no. 7621; pp. 548 - 552 |
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Main Authors | , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
22.09.2016
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Three papers in this issue of
Nature
use highly sensitive ChIP–seq assays to describe the dynamic patterns of histone modifications during early mouse embryogenesis, showing that oocytes have a distinctive epigenome and providing insights into how the maternal gene expression program transitions to the zygotic program.
Chromatin states in embryogenesis
Genomic analysis of chromatin states in early embryos has been technically difficult, owing to the limited number of cells available for analysis. Three papers in this issue of
Nature
use highly sensitive ChIP–seq assays to describe the dynamic patterns of histone modifications during early mouse embryogenesis. Arne Klungland and colleagues find that the oocyte genome is associated with broad non-canonical domains of histone H3K4me3 which seem to function in preventing deposition of DNA methylation. Wei Xie and colleagues find that the oocyte genome is associated with broad non-canonical domains of histone H3K4me3 which overlap with domains of low DNA methylation and seem to contribute to gene silencing. Shaorong Gao and colleagues map histone H3K4me3 and H3K27me3 modifications in pre-implantation embryos and focus on the re-establishment of histone modifications during zygotic genome activation. They find that the breadth of H3K4me3 domains is highly dynamic and that H3K4me3 re-establishes rapidly on promoter regions whereas H3K27me3 is mostly absent from these regions. Taken together—and with previously published work—these studies show that the oocyte has a distinctive epigenome and provide insights into how the maternal gene expression program transitions to the zygotic program.
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 embryogenesis
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. Dynamic histone modifications may have important roles in MZT
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, 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 steps
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or require a highly specialized microfluidics device that is not readily available
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. 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
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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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author Contributions J.A.D., I. Jung, B.R., and A.K. conceived the study. J.A.D. led the experiments with assistance from I. Jung, G.D.G., A.M., G.L., S.P, A.Y.L., I.J., M.H.H. and R.S. J.A.D. developed μChIP-seq, performed μChIP-seq with oocytes and embryos. J.A.D., A.M., I.J. and R.S. collected and prepared embryos, growing and mature oocytes. K.TD. and M.B. supervised the mouse work. M.H.H., A.M.and J.A.D. performed western blot. G.D.G. performed and J.A.D. and PF. supervised knockdown experiments and time laps imaging. G.D.G. performed I.F. with assistance from A.M. I. Jung performed RNA-seq with assistance from S.P I. Jung and G.L. performed WGBS. I. Jung led the data analysis with assistance from H.A. and M.L. K.H. supervised data analysis by M.L. S.K. and B. L. operated sequencing instruments and data processing. J.A.D. and I. Jung prepared the manuscript with assistance from H.A., M.L., B.R., and A.K. All authors read and commented on the manuscript. |
ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/nature19360 |