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Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues
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Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues
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Journal Article
Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues
2012
Overview
Amos Tanay and colleagues characterize DNA methylation polymorphism within cell populations and track immortalized fibroblasts in culture for over 300 generations to show that formation of differentially methylated regions occurs through a stochastic process and nearly deterministic epigenetic remodeling.
DNA methylation has been comprehensively profiled in normal and cancer cells, but the dynamics that form, maintain and reprogram differentially methylated regions remain enigmatic. Here, we show that methylation patterns within populations of cells from individual somatic tissues are heterogeneous and polymorphic. Using
in vitro
evolution of immortalized fibroblasts for over 300 generations, we track the dynamics of polymorphic methylation at regions developing significant differential methylation on average. The data indicate that changes in population-averaged methylation occur through a stochastic process that generates a stream of local and uncorrelated methylation aberrations. Despite the stochastic nature of the process, nearly deterministic epigenetic remodeling emerges on average at loci that lose or gain resistance to methylation accumulation. Changes in the susceptibility to methylation accumulation are correlated with changes in histone modification and CTCF occupancy. Characterizing epigenomic polymorphism within cell populations is therefore critical to understanding methylation dynamics in normal and cancer cells.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Biological and medical sciences
/ Cancer
/ Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
/ DNA
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation, Neoplastic
/ Genetics
/ Genetics of eukaryotes. Biological and molecular evolution
/ Humans
/ Molecular and cellular biology
/ Repressor Proteins - genetics
/ Repressor Proteins - metabolism
