Broadening our understanding of the genetics of Juvenile Idiopathic Arthritis (JIA): Interrogation of three dimensional chromatin structures and genetic regulatory elements within JIA-associated risk loci.

ABSTRACT:

Objective

The risk loci for juvenile idiopathic arthritis (JIA) consist of extended haplotypes that include functional elements in addition to canonical coding genes. As with most autoimmune diseases, the risk haplotypes for JIA are highly enriched for H3K4me1/H3K27ac histone marks, epigenetic signatures that typically identify poised or active enhancers. In this study, we test the hypothesis that genetic risk for JIA is exerted through altered enhancer-mediated gene regulation.

Methods

We mined publically available HiC and other chromatin conformation data to determine whether H3K27ac-marked regions in 25 JIA risk loci showed physical evidence of contact with gene promoters. We also used in vitro reporter assays to establish as proof-of-concept the idea that genetic variant

SUBMITTER: Jiang K 

PROVIDER: S-EPMC7392255 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature