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DNA methylation and gene expression

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Abstract Methylation of cytosines is the key epigenetic modification of DNA in eukaryotes and is associated with a repressed chromatin state and inhibition of gene expression. The methylation pattern in mammalian genomes is bimodal, with most of the genomes methylated except for short DNA stretches called CpG islands (CGIs), which are generally protected from methylation. Recent technical advances have made it possible to map DNA methylation patterns on a large scale. Several genomic studies have made significant progress in unraveling the intricate relationships between DNA methylation, chromatin structure, and gene expression. What is emerging is a more dynamic and complex association between DNA methylation and expression than previously known. Here we highlight several recent genomic studies with an emphasis on what new information is gained from these studies and what conclusions can be reached about the role of DNA methylation in controlling gene expression. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Biological Mechanisms > Regulatory Biology

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Different criterion for CGI definition. Four methods for definition of CGIs are illustrated. For each method a representative sequence of CGI and non‐CGI is shown. The main feature for discriminating CGIs in each method is highlighted in red. Red circles represent CXXC3 binding domain.

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Schematic representation of RNA polymerase II binding in different classes of promoter CGIs. The major chromatin patterns of promoter CGIs are shown, and their relative abundance is depicted by the area of the pie charts. The majority of CGIs (74%) are DNA unmethylated (unfilled circles), with open chromatin structure. Of these CGIs most (79%) are positive for RNA polymerase II binding. The second group (16%) represents the bivalent domain promoters. Of this group only 28% are positive for RNA polymerase II binding. The third and smallest group (7%) represents CGI promoters that are DNA methylated (filled circles). There is no clear correlation between this group and any specific chromatin marks (thus lacking triangles and flags). However, only 9% of these promoters are occupied by RNA polymerase II. (The data summarized in this figure is derived from the data published by Ref 24 regarding ES cells and NPCs).

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