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Development. 2017 Sep 15;144(18):3264-3277. doi: 10.1242/dev.155473. Epub 2017 Aug 21.

Maternal expression of the histone demethylase Kdm4a is crucial for pre-implantation development.

Author information

1
Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen 2200, Denmark.
2
Centre for Epigenetics, University of Copenhagen, Copenhagen 2200, Denmark.
3
The Danish Stem Cell Center (Danstem), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
4
Core Facility for Transgenic Mice, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
5
Department of Physiology Turku Center for Disease Modeling (TCDM), Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
6
Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg 41345, Sweden.
7
Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen 2200, Denmark kristian.helin@bric.ku.dk.

Abstract

Regulation of chromatin composition through post-translational modifications of histones contributes to transcriptional regulation and is essential for many cellular processes, including differentiation and development. KDM4A (JMJD2A) is a lysine demethylase with specificity towards di- and tri-methylated lysine 9 and lysine 36 of histone H3 (H3K9me2/me3 and H3K36me2/me3). Here, we report that Kdm4a as a maternal factor plays a key role in embryo survival and is vital for female fertility. Kdm4a-/- female mice ovulate normally with comparable fertilization but poor implantation rates, and cannot support healthy transplanted embryos to term. This is due to a role for Kdm4a in uterine function, where its loss causes reduced expression of key genes involved in ion transport, nutrient supply and cytokine signalling, which impact embryo survival. In addition, a significant proportion of Kdm4a-deficient oocytes displays a poor intrinsic ability to develop into blastocysts. These embryos cannot compete with healthy embryos for implantation in vivo, highlighting Kdm4a as a maternal effect gene. Thus, our study dissects an important dual role for maternal Kdm4a in determining faithful early embryonic development and the implantation process.

KEYWORDS:

Epigenetics; Female fertility; Histone demethylase; Maternal effect; Pre-implantation development; Transcription

PMID:
28827393
DOI:
10.1242/dev.155473
[Indexed for MEDLINE]
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