Bistable CpG-islands in an open sea of methylation

by Cecilia Lövkvist (Niels Bohr Institute)

Friday 27 Sept 2013, 13:00 → 14:00 Europe/Stockholm

RB35 (House 16, AlbaNova campus)

Stable inheritance of methylated CpG islands is needed for maintaining early developmental decisions in vertebrae. After replication maintenance methylases are turning hemi-methylated CpGs back to fully methylated and de novo methylases are turning unmethylated CpGs into hemi-methylated. The standard model proposes the methylases to act independently on the CpGs, however stochastic simulations shows that a stable methylation is not maintained with this property. Result from simulations for many generations is inconsistent with many experiments and observations. We therefore propose a collaborative model were CpGs are dependent on the surrounding CpGs. The dynamic collaboration between the CpG sites gives a stable bimodal pattern for the CpG-islands which is more consistent with experimental results. Additionally, the majority of the CpGs outside CpG-islands are often methylated. We find that demethylation is needed for keeping a bimodal pattern for a CpG-island within an open sea of methylated CpGs.