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Nat Commun. 2014 Dec 18;5:5868. doi: 10.1038/ncomms6868.

Paternal heterochromatin formation in human embryos is H3K9/HP1 directed and primed by sperm-derived histone modifications.

Author information

1
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
2
1] Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands [2] Department of Reproduction and Development, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
3
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
4
Department of Reproduction and Development, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
5
1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland [2] Faculty of Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.

Abstract

The different configurations of maternal and paternal chromatin, acquired during oogenesis and spermatogenesis, have to be rearranged after fertilization to form a functional embryonic genome. In the paternal genome, nucleosomal chromatin domains are re-established after the protamine-to-histone exchange. We investigated the formation of constitutive heterochromatin (cHC) in human preimplantation embryos. Our results show that histones carrying canonical cHC modifications are retained in cHC regions of sperm chromatin. These modified histones are transmitted to the oocyte and contribute to the formation of paternal embryonic cHC. Subsequently, the modifications are recognized by the H3K9/HP1 pathway maternal chromatin modifiers and propagated over the embryonic cleavage divisions. These results are in contrast to what has been described for mouse embryos, in which paternal cHC lacks canonical modifications and is initially established by Polycomb group proteins. Our results show intergenerational epigenetic inheritance of the cHC structure in human embryos.

PMID:
25519718
PMCID:
PMC4284653
DOI:
10.1038/ncomms6868
[Indexed for MEDLINE]
Free PMC Article

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