The RFTS (replication foci targeting sequence) domain of Dnmt1 is not only necessary for replication-coupled maintenance DNA methylation, but also protects genome from aberrant DNA methylation.

In mammals, DNA methylation plays important roles in embryogenesis and terminal differentiation via regulation of the transcription-competent chromatin state. The methylation patterns are propagated to the next generation during replication by maintenance DNA methyltransferase, Dnmt1, in co-operation with Uhrf1.
In the report, the contributions of the PCNA binding domain in the N-terminal domain and the RFTS domain to the maintenance DNA methylation process in mouse embryonic stem cells were examined. We found that the PCNA binding domain is dispensable and that the RFTS domain is necessary for the replication-coupled DNA methylation. Furthermore, the RFTS domain functions as a safety lock by protecting the genome from replication-independent DNA methylation.



Dual functions of the RFTS domain of Dnmt1 in replication-coupled DNA methylation and in protection of the genome from aberrant methylation. Ronald Garingalao Garvilles, Takashi Hasegawa, Hironobu Kimura, Jafar Sharif, Masahiro Muto, Haruhiko Koseki, Saori Takahashi, Isao Suetake, and Shoji Tajima
PLoS ONE 10(9): e0137509 2015. DOI:10.1371/journal.pone.0137509.



Contact: Shoji Tajima