| First Author | Sankar A | Year | 2017 |
| Journal | Development | Volume | 144 |
| Issue | 18 | Pages | 3264-3277 |
| PubMed ID | 28827393 | Mgi Jnum | J:245927 |
| Mgi Id | MGI:5918046 | Doi | 10.1242/dev.155473 |
| Citation | Sankar A, et al. (2017) Maternal expression of the histone demethylase Kdm4a is crucial for pre-implantation development. Development 144(18):3264-3277 |
| abstractText | 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. |
