Multidimensional mapping of stimulation-responsive regulatory elements and candidate causal variants in T cell activation.

ABSTRACT: Genome-wide association studies (GWASs) have elucidated numerous noncoding variants linked to immune-related disorders, yet the intricate context-specific mechanisms governing their effects remain poorly defined. Here, we leverage CD4⁺ T cell activation as a model to integrate multilayered genomic data and interrogate the dynamic regulatory mechanisms underpinning these genetic associations. We have applied a cistromic strategy to systematically identify and prioritize stimulation-responsive cis-regulatory elements (CREs) and key genes essential for T cell activation. Using capture Hi-C and tiling CRISPR activation screening at the CD28 locus, we reveal a pivotal CRE harboring a causal small insertion variant, rs5837875, that modulates CD28 activation in an allele-

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12757029 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature