Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

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

01/15/2014

Pubmed ID

24420542

Pubmed Central ID

PMC4315612

DOI

10.1161/HYPERTENSIONAHA.113.02637

Scopus ID

2-s2.0-84897061863   45 Citations

Abstract

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 M

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Mingyu Liang PhD Center Director, Professor in the Physiology department at Medical College of Wisconsin
Pengyuan Liu PhD Adjunct Professor in the Physiology department at Medical College of Wisconsin
Yong Liu PhD Assistant Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

5-Methylcytosine
Animals
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
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d