Comprehensive analysis of CpG islands in human chromosomes 21 and 22

TLDR

CpG islands are DNA regions enriched in CG dinucleotides, often found in gene promoters and implicated in gene silencing, but their definition (≥200 bp, ≥50 % GC, CpG/expected > 0.6) is arbitrary and may include non‑regulatory sequences. The study aims to analyze CpG island properties across human chromosomes 21 and 22 using a custom search algorithm. The algorithm identifies regions >500 bp with ≥55 % GC and CpG/expected ≥0.65, thereby favoring 5′ gene regions while excluding most Alu repeats. CpG suppression is pronounced in the human genome, modest in *Drosophila melanogaster* and *Saccharomyces cerevisiae*, consistent with 5‑methylcytosine detection in flies and suggesting possible CpG methylation in yeast. Mol.

Abstract

CpG islands are useful markers for genes in organisms containing 5-methylcytosine in their genomes. In addition, CpG islands located in the promoter regions of genes can play important roles in gene silencing during processes such as X-chromosome inactivation, imprinting, and silencing of intragenomic parasites. The generally accepted definition of what constitutes a CpG island was proposed in 1987 by Gardiner-Garden and Frommer [Gardiner-Garden, M. & Frommer, M. (1987) J. Mol. Biol. 196, 261–282] as being a 200-bp stretch of DNA with a C+G content of 50% and an observed CpG/expected CpG in excess of 0.6. Any definition of a CpG island is somewhat arbitrary, and this one, which was derived before the sequencing of mammalian genomes, will include many sequences that are not necessarily associated with controlling regions of genes but rather are associated with intragenomic parasites. We have therefore used the complete genomic sequences of human chromosomes 21 and 22 to examine the properties of CpG islands in different sequence classes by using a search algorithm that we have developed. Regions of DNA of greater than 500 bp with a G+C equal to or greater than 55% and observed CpG/expected CpG of 0.65 were more likely to be associated with the 5′ regions of genes and this definition excluded most Alu -repetitive elements. We also used genome sequences to show strong CpG suppression in the human genome and slight suppression in Drosophila melanogaster and Saccharomyces cerevisiae . This finding is compatible with the recent detection of 5-methylcytosine in Drosophila , and might suggest that S. cerevisiae has, or once had, CpG methylation.