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Mech Ageing Dev. 2014 Jan;135:50-6. doi: 10.1016/j.mad.2014.01.005. Epub 2014 Jan 23.

Splicing factor 3B1 hypomethylation is associated with altered SF3B1 transcript expression in older humans.

Author information

1
Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
2
Epidemiology and Public Health, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
3
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
4
National Institute on Aging, Clinical Research Branch, Harbor Hospital, Baltimore, MD 21225, USA.
5
Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK. Electronic address: L.W.Harries@exeter.ac.uk.

Abstract

Ageing in man is associated with changes to the splicing factor pool. A proportion of splicing factors are regulated during ageing by mechanisms involving the Ataxia Telangiectasia Mutated (ATM) gene, but the factors that determine the remaining proportion have yet to be identified. DNA methylation is known to be an important regulatory mechanism of gene expression. We assessed age-associated methylation and expression levels for 27 splicing factor genes, in peripheral blood samples from the InCHIANTI study. Examination of splicing patterns at specific loci was examined in a second cohort, the Exeter 10000 study. 27/502 methylation probes in 17 different genes were associated with age. Most changes were not associated with transcript expression levels or splicing patterns, but hypomethylation of the SF3B1 promoter region was found to mediate 53% of the relationship between age and transcript expression at this locus (p=0.02). DNA methylation does not appear to play a major role in regulation of the splicing factors, but changes in SF3B1 expression may be attributable to promoter hypomethylation at this locus. SF3B1 encodes a critical component of the U2 snRNP; altered expression of this gene may therefore contribute to the loss of regulated mRNA splicing that occurs with age.

KEYWORDS:

Ageing; DNA methylation; Epigenetics; SF3B1; Splicing

PMID:
24463145
PMCID:
PMC5985527
DOI:
10.1016/j.mad.2014.01.005
[Indexed for MEDLINE]
Free PMC Article

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