Gene silencing in mammalian cells and the spread of DNA methylation

Abstract

Aberrant gene silencing in mammalian cells is associated with promoter region methylation, but the sequence of these two events is not clear. This review will consider the possibility that gene silencing is not a single event, but instead a series of events that begins with a dramatic drop in transcription potential and ends with its complete cessation. This transition will be portrayed as a chaotic process that ensues when transcription levels drop and DNA methylation begins spreading haltingly towards the diminished promoter. According to this view, silencing is stabilized when the promoter region is 'captured' by the spread of DNA methylation near or into its transcription factor binding sites.