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Publication : Methionine adenosyltransferase 2A regulates mouse zygotic genome activation and morula to blastocyst transition†.

First Author  Sun H Year  2019
Journal  Biol Reprod Volume  100
Issue  3 Pages  601-617
PubMed ID  30265288 Mgi Jnum  J:277733
Mgi Id  MGI:6316948 Doi  10.1093/biolre/ioy194
Citation  Sun H, et al. (2019) Methionine adenosyltransferase 2A regulates mouse zygotic genome activation and morula to blastocyst transition. Biol Reprod 100(3):601-617
abstractText  Methionine adenosyltransferase II (MAT2A) is essential to the synthesis of S-adenosylmethionine, a major methyl donor, from L-methionine and ATP. Upon fertilization, zygotic genome activation (ZGA) marks the period that transforms the genome from transcriptional quiescence to robust transcriptional activity. During this period, embryonic epigenome undergoes extensive modifications, including histone methylation changes. However, whether MAT2A participates in histone methylation at the ZGA stage is unknown. Herein, we identified that MAT2A is a pivotal factor for ZGA in mouse embryos. Mat2a knockdown exhibited 2-cell embryo arrest and reduced transcriptional activity but did not affect H3K4me2/3 and H3K9me2/3. When the cycloleucine, a selective inhibitor of MAT2A catalytic activity, was added to a culture medium, embryos were arrested at the morula stage in the same manner as the embryos cultured in an L-methionine-deficient medium. Under these two culture conditions, H3K4me3 levels of morula and blastocyst were much lower than those cultured under normal medium. Furthermore, cycloleucine treatment or methionine starvation apparently reduced the developmental potential of blastocysts. Thus, Mat2a is indispensable for ZGA and morula-to-blastocyst transition.
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