Premium
Base‐resolution maps of 5‐methylcytosine and 5‐hydroxymethylcytosine in Dahl salt‐sensitive rats (1120.8)
Author(s) -
Liu Yong,
Liu Pengyuan,
Yang Chun,
Cowley Allen,
Liang Mingyu
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1120.8
Subject(s) - 5 methylcytosine , cpg site , dna methylation , 5 hydroxymethylcytosine , biology , epigenetics , methylation , gene , genetics , microbiology and biotechnology , gene expression
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 SS 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 lower in genes with lower expression. Substitution of a 12.9 Mbp region of chromosome 13, which attenuates the hypertensive and renal injury phenotypes in SS rats, or exposure to a high‐salt diet, which induces 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 DNA methylation. The study established base resolution maps of 5mC and 5hmC in an in vivo model of disease and revealed several characteristics important for understanding the contribution of 5mC and 5hmC to hypertension and other complex diseases. Grant Funding Source : Supported by the NIH.