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

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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Inoue A,Chen Z,Yin Q,Zhang Y

doi

10.1101/gad.318675.118

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

1525-1536

issue

23-24

eissn

0890-9369

issn

1549-5477

pii

gad.318675.118

journal_volume

32

pub_type

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