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Sequence determinants, function, and evolution of CpG islands

Abstract

In vertebrates, cytosine-guanine (CpG) dinucleotides are predominantly methylated, with approximately 80% of all CpG sites containing 5-methylcytosine (5mC), a repressive mark associated with long-term gene silencing. The exceptions to such a globally hypermethylated state are CpG-rich DNA sequences called CpG islands (CGIs), which are mostly hypomethylated relative to the bulk genome. CGIs overlap promoters from the earliest vertebrates to humans, indicating a concerted evolutionary drive compatible with CGI retention. CGIs are characterised by DNA sequence features that include DNA hypomethylation, elevated CpG and GC content and the presence of transcription factor binding sites. These sequence characteristics are congruous with the recruitment of transcription factors and chromatin modifying enzymes, and transcriptional activation in general. CGIs colocalize with sites of transcriptional initiation in hypermethylated vertebrate genomes, however, a growing body of evidence indicates that CGIs might exert their gene regulatory function in other genomic contexts. In this review, we discuss the diverse regulatory features of CGIs, their functional readout, and the evolutionary implications associated with CGI retention in vertebrates and possibly in invertebrates.

Type Journal
ISBN 1470-8752 (Electronic) 0300-5127 (Linking)
Authors Angeloni, A.; Bogdanovic, O.
Responsible Garvan Author A/Prof Ozren Bogdanovic
Publisher Name BIOCHEMICAL SOCIETY TRANSACTIONS
Published Date 2021-06-30
Published Volume 49
Published Issue 3
Published Pages 1109-1119
Status Published in-print
DOI 10.1042/BST20200695
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/34156435