Functions of Dot1-Mediated Histone H3 Methylation

<p>Two models for the role of Dot1-mediated methylation of histone H3 are diagrammed, comparing a Dot1 mutant (ΔDot1) and a wild-type cell. The repulsion model is derived from [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060185#pbio-0060185-b021" target="_blank">21</a>]. Methylation of histone H3 is indicated by “me”, and the level of transcription of a chromosome (black line) is indicated by a shaded gray bar (a thick bar indicates active transcription, a thin bar indicates silenced transcription). Silencing factors (such as Sir proteins in yeast; light blue circles) are indicated localised to the telomere (vertical line) in wild-type cells, being excluded from elsewhere by H3K79 methylation. Mutation of Dot1 removes H3K79 methylation, de-repressing transcription of the telomeric region. The recruitment model is based on [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060185#pbio-0060185-b032" target="_blank">32</a>], and shows the same region of chromosome after suffering a DNA double-strand break (gap in the line). Here, histone H3K79 methylation recruits a checkpoint signalling factor (Rad9 in yeast; dark blue circle), and in the absence of histone H3K79 methylation processing of the DNA break to yield single stranded DNA is increased, amplifying the DNA damage signalling cascade.