Base-resolution maps of 5-methylcytosine and 5-hydroxymethylcytosine in Dahl S rats: effect of salt and genomic sequence. Hypertension 2014 Apr;63(4):827-38
Date
01/15/2014Pubmed ID
24420542Pubmed Central ID
PMC4315612DOI
10.1161/HYPERTENSIONAHA.113.02637Scopus ID
2-s2.0-84897061863 (requires institutional sign-in at Scopus site) 61 CitationsAbstract
Analysis of 5-hydroxymethylcytosine (5hmC) at single-base resolution has been largely limited to studies of stem cells or developmental stages. Given the potential importance of epigenetic events in hypertension, we have analyzed 5hmC and 5-methylcytosine (5mC) at single-base resolution in the renal outer medulla of the Dahl salt-sensitive rat and examined the effect of disease-relevant genetic or environmental alterations on 5hmC and 5mC patterns. Of CpG sites that fell within CpG islands, 11% and 1% contained significant 5mC and 5hmC, respectively. 5mC levels were substantially higher for genes with lower mRNA abundance and showed a prominent nadir around the transcription start site. In contrast, 5hmC levels were higher in genes with higher expression. Substitution of a 12.9-Mbp region of chromosome 13, which attenuates the hypertensive and renal injury phenotypes in salt-sensitive rats, or exposure to a high-salt diet, which accelerates the disease phenotypes, was associated with differential 5mC or 5hmC in several hundred CpG islands. Nearly 80% of the CpG islands that were differentially methylated in response to salt and associated with differential mRNA abundance were intragenic CpG islands. The substituted genomic segment had significant cis effects on mRNA abundance but not on DNA methylation. The study established base-resolution maps of 5mC and 5hmC in an in vivo model of disease and revealed several characteristics of 5mC and 5hmC important for understanding the role of epigenetic modifications in the regulation of organ systems function and complex diseases.
Author List
Liu Y, Liu P, Yang C, Cowley AW Jr, Liang MAuthor
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
5-MethylcytosineAnimals
Base Sequence
CpG Islands
Cytosine
Disease Models, Animal
Epigenomics
Genome-Wide Association Study
Hypertension
Kidney Medulla
Male
Phenotype
RNA, Messenger
Rats
Rats, Inbred Dahl
Sodium Chloride, Dietary
Transcriptome
