Genome-wide map of proximity linkage to renin proximal promoter in rat. Physiol Genomics 2018 May 01;50(5):323-331
Date
03/10/2018Pubmed ID
29521603Pubmed Central ID
PMC6008118DOI
10.1152/physiolgenomics.00132.2017Scopus ID
2-s2.0-85061579448 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
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 MAuthor
Aron Geurts PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood 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
