RT Journal Article
SR Electronic
T1 Chromosome contacts in activated T cells identify autoimmune disease-candidate genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 100958
DO 10.1101/100958
A1 Oliver S Burren
A1 Arcadio Rubio García
A1 Biola-Maria Javierre
A1 Daniel B Rainbow
A1 Jonathan Cairns
A1 Nicholas J Cooper
A1 John J Lambourne
A1 Ellen Schofield
A1 Xaquin Castro Dopico
A1 Ricardo C Ferreira
A1 Richard Coulson
A1 Frances Burden
A1 Sophia P Rowlston
A1 Kate Downes
A1 Steven W Wingett
A1 Mattia Frontini
A1 Willem H Ouwehand
A1 Peter Fraser
A1 Mikhail Spivakov
A1 John A Todd
A1 Linda S Wicker
A1 Antony J Cutler
A1 Chris Wallace
YR 2017
UL http://biorxiv.org/content/early/2017/01/17/100958.abstract
AB Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4+ T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes. Here we show that, within four hours, activation of CD4+ T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C (PCHi-C). By integrating PCHi-C data with genetic associations for five autoimmune diseases we prioritised 252 candidate genes, of which 116 were related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach.