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DNA hypermethylation of alternatively spliced and repeat sequences in humans.

ΤίτλοςDNA hypermethylation of alternatively spliced and repeat sequences in humans.
Publication TypeJournal Article
Year of Publication2012
AuthorsMalousi, A., & Kouidou S.
JournalMol Genet Genomics
Volume287
Issue8
Pagination631-42
Date Published2012 Aug
ISSN1617-4623
Λέξεις κλειδιάAlternative Splicing, Chromosomes, Human, Pair 20, Chromosomes, Human, Pair 22, Chromosomes, Human, Pair 6, Computational Biology, DNA Methylation, Humans, Repetitive Sequences, Nucleic Acid, RNA Splice Sites, Transcription, Genetic
Abstract

DNA methylation is presently accepted as a tentative regulatory parameter in splicing. Recently, we reported significant methylation differences among various exonic splicing-enhancing elements and alternative splicing events, based on CpG methylation data from the Human Epigenome Project for chromosomes 6, 20 and 22. Presently, using a different computational approach and the same database, we report: (a) significant increase of hypermethylation in intronic and exonic sequences close to acceptor sites, relative to overall introns and exons, respectively (1,973 CpGs examined); (b) frequent CpGs, mostly hypomethylated, in donors and infrequent CpGs mostly hypermethylated, in acceptors; and (c) hypermethylation in cassette exons which are occasionally spliced and have weaker average splicing potential, relative to constitutive exons (p < 0.0001). CpGs are hypomethylated in non-coding exons (only 16 % hypermethylation). Single-exon genes, similarly to first exons, frequently contain hypomethylated CpGs, while in internal and last exons CpGs are more frequently hypermethylated. Methylation is also more frequent in strange introns and splice sites processed by the minor spliceosome, e.g., ATAC, (p < 0.0001 in all cases), but not in sites of incomplete processing, e.g., retained introns or bleeding exons, (p = 0.706 and p = 0.313, respectively). Most Alus, which are known to contribute to transcript presentation, are heavily methylated, in contrast with other Alus, e.g., AluJo and mammalian interspersed repetitive elements which have been previously associated with alternative expression. These results elucidate the role of intragenic methylation in association with alternative splicing and facilitate the evaluation of genomic variations/polymorphisms and the development of tools for the prediction of alternative splicing events.

DOI10.1007/s00438-012-0703-y
Alternate JournalMol. Genet. Genomics
PubMed ID22740315
PubMed Central IDPMC3407362

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