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

TY - JOUR

T1 - Maternal expression of the histone demethylase Kdm4a is crucial for pre-implantation development

AU - Sankar, Aditya

AU - Kooistra, Susanne Marije

AU - Gonzalez, Javier Martin

AU - Ohlsson, Claes

AU - Poutanen, Matti

AU - Helin, Kristian

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Epigenetics

KW - Female fertility

KW - Histone demethylase

KW - Maternal effect

KW - Pre-implantation development

KW - Transcription

U2 - 10.1242/dev.155473

DO - 10.1242/dev.155473

M3 - Journal article

C2 - 28827393

AN - SCOPUS:85029820784

SN - 0950-1991

VL - 144

SP - 3264

EP - 3277

JO - Development (Cambridge)

JF - Development (Cambridge)

IS - 18

ER -