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Genes Dev. 2018 Dec 1;32(23-24):1525-1536. doi: 10.1101/gad.318675.118. Epub 2018 Nov 21.

Maternal Eed knockout causes loss of H3K27me3 imprinting and random X inactivation in the extraembryonic cells.

Inoue A#1,2,3, Chen Z#1,2,3, Yin Q1,2,3, Zhang Y1,2,3,4,5.

Author information

1
Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
2
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
3
Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
4
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
5
Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA.
#
Contributed equally

Abstract

Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 Lys27 trimethylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we demonstrate that maternal Eed, an essential component of the Polycomb group complex 2 (PRC2), is required for establishing H3K27me3 imprinting. We found that all H3K27me3-imprinted genes, including Xist, lose their imprinted expression in Eed maternal knockout (matKO) embryos, resulting in male-biased lethality. Surprisingly, although maternal X-chromosome inactivation (XmCI) occurs in Eed matKO embryos at preimplantation due to loss of Xist imprinting, it is resolved at peri-implantation. Ultimately, both X chromosomes are reactivated in the embryonic cell lineage prior to random XCI, and only a single X chromosome undergoes random XCI in the extraembryonic cell lineage. Thus, our study not only demonstrates an essential role of Eed in H3K27me3 imprinting establishment but also reveals a unique XCI dynamic in the absence of Xist imprinting.

KEYWORDS:

H3K27me3; Polycomb; X chromosome inactivation; genomic imprinting; mouse early development

PMID:
30463900
PMCID:
PMC6295166
DOI:
10.1101/gad.318675.118
[Indexed for MEDLINE]
Free PMC Article

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