DNA Methyltransferases: Facts, Clues, Mysteries

DNA methylation plays a pivotal role during development in mammals and is central to transcriptional silencing. The DNA methyltransferases (DNMTs) are respon- sible for the generation of genomic methylation patterns leading to gene silencing, but the underlying molecular basis remains largely shrouded in mystery. Here we review our current understanding of the mechanisms by which DNMTs repress transcription and how they are targeted to preferred DNA sequences. Emerging evidence points to an essential and intricate web of interactions between DNMTs and the chromatin environment in which they function. The recent identification of novel transcription factors recruiting the DNMTs may open new avenues of research into the origin of DNA methylation patterns. Thanks to these emerging clues, researchers have begun to lift the veil on the multi-faceted DNMTs, but there remains fascinating work ahead for whoever wants to fully understand DNMTs and their role in the mammalian cell.