Histone modifications control DNA methylation profiles during ageing and tumour expansion

The stem cell epigenome reflects a delicate balance of chromatin (de-)modification processes. During cancer development this balance becomes disturbed, resulting in characteristic changes. Among them are changes of the DNA methylation profile. It has been demonstrated that these changes share common features with changes observed during stem cell ageing. Recently, we proposed that chromatin remodelling during stem cell ageing originates in the limited cellular capability to inherit histone modification states, and thus is linked to cell proliferation. This suggests that increased proliferation activity and associated loss of histone modification may represent a generic cause of the changes observed in cancer DNA methylation profiles. Moreover, additional changes of these profiles due to mutations of chromatin modifiers are expected to act on this background. We study the implications of these assumptions, introducing a computational model which describes transcriptional regulation by cis-regulatory networ...