News Releases & Research Results Discovery of specific functions of DNA methyltransferases, DNMT3A and DNMT3B - Contributing to the elucidation of mammalian development and cancer development mechanisms -

The results of collaborative research conducted by the research group of Research Fellow Masaki Yagi of Harvard University (formerly Assistant Professor of Division of Stem Cell Pathology, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo), Professor Yasuhiro Yamada of Division of Stem Cell Pathology, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, the University of Tokyo, Technical Staff Mio Kabata, Associate Professor Takuya Yamamoto of the Center for iPS Cell Research and Application (CiRA), Kyoto University, and others.

• Regarding de novo DNA methylation*, whose alteration is greatly related to the cause of cancer development, the research succeeded in identifying the specific target site of DNA methyltransferases, DNMT3A and DNMT3B, for the first time in the world through the experiment using DNA hypomethylated ES cells, and partly clarified the mechanism governing DNA methylation during mammalian development. *: A chemical reaction wherein a methyl group is added mainly in the CG site in the DNA. It is essential for mammalian ontogeny and its abnormalities cause cancers such as leukemia.
• In addition, the research group revealed that DNMT3A specifically methylates the developmental genes and DNMT3B specifically methylates the X chromosomal genes, and succeeded in identifying hypomethylated regions characteristic of cancer/diseases with DNMT3 gene mutations.
• The results of this research should lead to the establishment of novel treatment methods for cancers with altered DNA methylation.

This research project was conducted with the support of the Advanced Research and Development Programs for Medical Innovation (AMED-CREST), Project for Cancer Research and Therapeutic Evolution (P-CREATE) by AMED.

The results of research were published online in Nature Communications on June 24.

Yagi M., et al. Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development Nature Communications
DOI: 10.1038/s41467-020-16989-w