Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Sep 22;537(7621):553-557.
doi: 10.1038/nature19361. Epub 2016 Sep 14.

Allelic reprogramming of the histone modification H3K4me3 in early mammalian development

Bingjie Zhang  1 , Hui Zheng  1 , Bo Huang  1   2 , Wenzhi Li  3 , Yunlong Xiang  1 , Xu Peng  4 , Jia Ming  3 , Xiaotong Wu  5 , Yu Zhang  1 , Qianhua Xu  1 , Wenqiang Liu  6 , Xiaochen Kou  6 , Yanhong Zhao  6 , Wenteng He  6 , Chong Li  6 , Bo Chen  3 , Yuanyuan Li  1 , Qiujun Wang  1 , Jing Ma  1 , Qiangzong Yin  1 , Kehkooi Kee  3 , Anming Meng  5 , Shaorong Gao  6 , Feng Xu  4   7 , Jie Na  3 , Wei Xie  1
Affiliations

Allelic reprogramming of the histone modification H3K4me3 in early mammalian development

Bingjie Zhang et al. Nature. .

Abstract

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.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Cell Sci. 2010 Dec 15;123(Pt 24):4292-300 - PubMed
    1. Int J Dev Biol. 2012;56(10-12):867-75 - PubMed
    1. Hum Reprod. 2002 Aug;17(8):2152-9 - PubMed
    1. Cell. 2013 May 9;153(4):759-72 - PubMed
    1. Nature. 2012 Aug 2;488(7409):116-20 - PubMed

Publication types

MeSH terms