Maternal expression of the histone demethylase Kdm4a is crucial for pre-implantation developmentSankar, A., Kooistra, S. M., Gonzalez, J. M., Ohlsson, C., Poutanen, M. & Helin, K., 15-Sep-2017, In : DEVELOPMENT. 144, 18, p. 3264-3277 14 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||14|
|Publication status||Published - 15-Sep-2017|
- Epigenetics, Female fertility, Histone demethylase, Pre-implantation development, Maternal effect, Transcription, HUMAN BREAST-CANCER, COLONY-STIMULATING FACTORS, ACUTE MYELOID-LEUKEMIA, FACTOR-DEFICIENT MICE, LUTEINIZING-HORMONE, TARGETED DISRUPTION, GENE-EXPRESSION, NULL MUTATION, JMJD2 FAMILY, IN-VITRO