Allelic reprogramming of the histone modification H3K4me3 in early mammalian development.
Histone modifications are fundamental epigenetic regulators that control many crucial cellular processes. However, whether these marks can be passed on from mammalian gametes to the next generation is a long-standing question that remains unanswered. Here, by developing a highly sensitive approach, STAR ChIP-seq, we provide a panoramic view of the landscape of H3K4me3, a histone hallmark for transcription initiation, from developing gametes to post-implantation embryos. We find that upon fertilization, extensive reprogramming occurs on the paternal genome, as H3K4me3 peaks are depleted in zygotes but are readily observed after major zygotic genome activation at the late two-cell stage. On the maternal genome, we unexpectedly find a non-canonical form of H3K4me3 (ncH3K4me3) in full-grown and mature oocytes, which exists as broad peaks at promoters and a large number of distal loci. Such broad H3K4me3 peaks are in contrast to the typical sharp H3K4me3 peaks restricted to CpG-rich regions of promoters. Notably, ncH3K4me3 in oocytes overlaps almost exclusively with partially methylated DNA domains. It is then inherited in pre-implantation embryos, before being erased in the late two-cell embryos, when canonical H3K4me3 starts to be established. The removal of ncH3K4me3 requires zygotic transcription but is independent of DNA replication-mediated passive dilution. Finally, downregulation of H3K4me3 in full-grown oocytes by overexpression of the H3K4me3 demethylase KDM5B is associated with defects in genome silencing. Taken together, these data unveil inheritance and highly dynamic reprogramming of the epigenome in early mammalian development.
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Bingjie
B
Zhang
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Hui
H
Zheng
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|PKU-THU Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
Bo
B
Huang
Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
Wenzhi
W
Li
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yunlong
Y
Xiang
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore 117609, Singapore.
Xu
X
Peng
Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
Jia
J
Ming
State Key Laboratory of Biomembrane and Membrane Engineering, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Xiaotong
X
Wu
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yu
Y
Zhang
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Qianhua
Q
Xu
Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Wenqiang
W
Liu
Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Xiaochen
X
Kou
Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Yanhong
Y
Zhao
Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Wenteng
W
He
Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Chong
C
Li
Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
Bo
B
Chen
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yuanyuan
Y
Li
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Qiujun
Q
Wang
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Jing
J
Ma
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Qiangzong
Q
Yin
Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
Kehkooi
K
Kee
State Key Laboratory of Biomembrane and Membrane Engineering, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Anming
A
Meng
Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Shaorong
S
Gao
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore 117609, Singapore.|Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore.
Feng
F
Xu
Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
Jie
J
Na
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Wei
W
Xie
D000483:Alleles; D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D005306:Fertilization / Q000235:genetics; D020868:Gene Silencing; D016678:Genome / Q000235:genetics; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008745:Methylation; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D061785:Transcription Initiation, Genetic; D015053:Zygote / Q000378:metabolism
D004268:DNA-Binding Proteins; D006657:Histones; D056484:Jumonji Domain-Containing Histone Demethylases; C485614:Kdm5b protein, mouse; D008239:Lysine