Dataset Information

CpG islands or CpG clusters: how to identify functional GC-rich regions in a genome?

ABSTRACT:

Background

CpG islands (CGIs), clusters of CpG dinucleotides in GC-rich regions, are often located in the 5' end of genes and considered gene markers. Hackenberg et al. (2006) recently developed a new algorithm, CpGcluster, which uses a completely different mathematical approach from previous traditional algorithms. Their evaluation suggests that CpGcluster provides a much more efficient approach to detecting functional clusters or islands of CpGs.

Results

We systematically compared CpGcluster with the traditional algorithm by Takai and Jones (2002). Our comparisons of (1) the number of islands versus the number of genes in a genome, (2) the distribution of islands in different genomic regions, (3) island length, (4) the distance between two neighboring islands, and (5) methylation status suggest that Takai and Jones' algorithm is overall more appropriate for identifying promoter-associated islands of CpGs in vertebrate genomes.

Conclusion

The generation of genome sequence and DNA methylation data is expected to accelerate greatly. The information in this study is important for its extensive utility in gene feature analysis and epigenomics including gene prediction and methylation chip design in different genomes.

SUBMITTER: Han L

PROVIDER: S-EPMC2652441 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Publications

CpG islands or CpG clusters: how to identify functional GC-rich regions in a genome?

Han Leng L Zhao Zhongming Z

BMC bioinformatics 20090220

<h4>Background</h4>CpG islands (CGIs), clusters of CpG dinucleotides in GC-rich regions, are often located in the 5' end of genes and considered gene markers. Hackenberg et al. (2006) recently developed a new algorithm, CpGcluster, which uses a completely different mathematical approach from previous traditional algorithms. Their evaluation suggests that CpGcluster provides a much more efficient approach to detecting functional clusters or islands of CpGs.<h4>Results</h4>We systematically compar ...[more]

PMID: 19232104

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Project description:BackgroundMammalian CpG islands (CGIs) normally escape DNA methylation in all adult tissues and developmental stages. However, in our previous study we unexpectedly identified many methylated CGIs in human peripheral blood leukocytes. Methylated CpG dinucleotides convert to TpG dinucleotides through deaminization of their cytosine bases more frequently than hypomethylated CpG dinucleotides. Therefore, we wondered how methylated CGIs in germline or non-germline cells maintain their CpG-rich sequences. It is known that events such as germline hypomethylation, CpG selection, biased gene conversion (BGC), and frequent CpG fixation can contribute to the maintenance of CpG-rich sequences in methylated CGIs in germline or non-germline cells. However, it has not been investigated which of the processes maintain CpG-rich sequences of methylated CGIs in each genomic position.ResultsIn this study, we comprehensively examined the contribution of the processes described above to the maintenance of CpG-rich sequences in methylated CGIs in germline and non-germline cells which were classified by genomic positions. Approximately 60-80% of CGIs with high methylation in H1 cell line (H1-HM) in all the genomic positions showed a low average CpG→TpG/CpA substitution rate. In contrast, fewer than half the numbers of CGIs with H1-HM in all the genomic positions showed a low average CpG→TpG/CpA substitution rate and low levels of methylation in sperm cells (SPM-LM). Furthermore, a small fraction of CGIs with a low average CpG→TpG/CpA substitution rate and high levels of methylation in sperm cells (SPM-HM) showed CpG selection. On the other hand, independent of the positions in genes, most CGIs with SPM-HM showed a slightly higher average TpG/CpA→CpG substitution rate compared with those with SPM-LM.ConclusionsRelatively high numbers (approximately 60-80%) of CGIs with H1-HM in all the genomic positions preserve their CpG-rich sequences by a low CpG→TpG/CpA substitution rate caused mainly by their SPM-LM, and for those with SPM-HM partly by CpG selection and TpG/CpA→CpG fixation. BGC has little contribution to the maintenance of CpG-rich sequences of CGIs with SPM-HM which were classified by genomic positions.

Project description:DNA methylation is a covalent modification of the nucleotide cytosine that is stably inherited at the dinucleotide CpG by somatic cells, and 70% of CpG dinucleotides in the genome are methylated. The exception to this pattern of methylation are CpG islands, CpG-rich sequences that are protected from methylation, and generally are thought to be methylated only on the inactive X-chromosome and in tumors, as well as differentially methylated regions (DMRs) in the vicinity of imprinted genes. To identify chromosomal regions that might harbor imprinted genes, we devised a strategy for isolating a library of normally methylated CpG islands. Most of the methylated CpG islands represented high copy number dispersed repeats. However, 62 unique clones in the library were characterized, all of which were methylated and GC-rich, with a GC content >50%. Of these, 43 clones also showed a CpG(obs)/CpG(exp) >0.6, of which 30 were studied in detail. These unique methylated CpG islands mapped to 23 chromosomal regions, and 12 were differentially methylated regions in uniparental tissues of germline origin, i.e., hydatidiform moles (paternal origin) and complete ovarian teratomas (maternal origin), even though many apparently were methylated in somatic tissues. We term these sequences gDMRs, for germline differentially methylated regions. At least two gDMRs mapped near imprinted genes, HYMA1 and a novel homolog of Elongin A and Elongin A2, which we term Elongin A3. Surprisingly, 18 of the methylated CpG islands were methylated in germline tissues of both parental origins, representing a previously uncharacterized class of normally methylated CpG islands in the genome, and which we term similarly methylated regions (SMRs). These SMRs, in contrast to the gDMRs, were significantly associated with telomeric band locations (P =.0008), suggesting a potential role for SMRs in chromosome organization. At least 10 of the methylated CpG islands were on average 85% conserved between mouse and human. These sequences will provide a valuable resource in the search for novel imprinted genes, for defining the molecular substrates of the normal methylome, and for identifying novel targets for mammalian chromatin formation.

Dataset Information

CpG islands or CpG clusters: how to identify functional GC-rich regions in a genome?

Background

Results

Conclusion

Publications

CpG islands or CpG clusters: how to identify functional GC-rich regions in a genome?

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