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.
| Original language | English |
|---|---|
| Journal | Development (Cambridge) |
| Volume | 144 |
| Issue number | 18 |
| Pages (from-to) | 3264-3277 |
| Number of pages | 14 |
| ISSN | 0950-1991 |
| DOIs | |
| Publication status | Published - 1 Jan 2017 |
Keywords
- Epigenetics
- Female fertility
- Histone demethylase
- Maternal effect
- Pre-implantation development
- Transcription