Allele-specific expression changes dynamically during T cell activation in HLA and other autoimmune loci.

ABSTRACT: Genetic studies have revealed that autoimmune susceptibility variants are over-represented in memory CD4⁺ T cell regulatory elements^1-3. Understanding how genetic variation affects gene expression in different T cell physiological states is essential for deciphering genetic mechanisms of autoimmunity^4,5. Here, we characterized the dynamics of genetic regulatory effects at eight time points during memory CD4⁺ T cell activation with high-depth RNA-seq in healthy individuals. We discovered widespread, dynamic allele-specific expression across the genome, where the balance of alleles changes over time. These genes were enriched fourfold within autoimmune loci. We found pervasive dynamic regulatory effects within six HLA genes. HLA-DQB1 alleles had on

SUBMITTER: Gutierrez-Arcelus M 

PROVIDER: S-EPMC7135372 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature