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Genome-wide map of proximity linkage to renin proximal promoter in rat. Physiol Genomics 2018 05 01;50(5):323-331

Date

03/10/2018

Pubmed ID

29521603

Pubmed Central ID

PMC6008118

DOI

10.1152/physiolgenomics.00132.2017

Scopus ID

2-s2.0-85061579448   4 Citations

Abstract

A challenge to understanding enhancer-gene relationships is that enhancers are not always sequentially close to the gene they regulate. Physical proximity mapping through sequencing can provide an unbiased view of the chromatin close to the proximal promoter of the renin gene ( Ren). Our objective was to determine genomic regions that physically interact with the renin proximal promoter, using two different genetic backgrounds, the Dahl salt sensitive and normotensive SS-13BN, which have been shown to have different regulation of plasma renin in vivo. The chromatin conformation capture method with sequencing focused at the Ren proximal promoter in rat-derived cardiac endothelial cells was used. Cells were fixed, chromatin close to the Ren promoter was captured, and fragments were sequenced. The clustering of mapped reads produced a genome-wide map of chromatin in contact with the Ren promoter. The largest number of contacts was found on chromosome 13, the chromosome with Ren, and contacts were found on all other chromosomes except chromosome X. These contacts were significantly enriched with genes positively correlated with Ren expression and with mapped quantitative trait loci associated with blood pressure, cardiovascular, and renal phenotypes. The results were reproducible in an independent biological replicate. The findings reported here represent the first map between a critical cardiovascular gene and physical interacting loci throughout the genome and will provide the basis for several new directions of research.

Author List

Stodola TJ, Liu P, Liu Y, Vallejos AK, Geurts AM, Greene AS, Liang M

Authors

Aron Geurts PhD Associate 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

Animals
Blood Pressure
Cells, Cultured
Chromosome Mapping
Chromosomes, Mammalian
Female
Gene Expression
Genome
Male
Promoter Regions, Genetic
Quantitative Trait Loci
Rats, Inbred BN
Rats, Inbred Dahl
Renin
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d