Author:
Gabele Anna,Sprang Maximilian,Cihan Mert,Dietzen Sarah,Klein Matthias,Harms Gregory,Ziesmann Tanja,Pape Katrin,Wasser Beatrice,Gomez-Zepeda David,Braband Kathrin,Delacher Michael,Lemmermann Niels,Bittner Stefan,Andrade-Navarro Miguel A.,Tenzer Stefan,Bopp Tobias,Distler Ute
Abstract
ABSTRACTThe transcription factor interferon regulatory factor 4 (IRF4) is crucial for the differentiation and fate determination of pro-inflammatory T helper (Th)17 and the functionally opposing group of immunomodulatory regulatory T (Treg) cells. However, molecular mechanisms of how IRF4 steers diverse transcriptional programs in Th17 and Treg cells are far from being definitive. To unveil IRF4-driven lineage determination in Th17 and Treg cells, we integrated data derived from affinity-purification and full mass spectrometry-based proteome analysis with chromatin immune precipitation sequencing (ChIP-Seq). This allowed the characterization of subtype-specific molecular programs and the identification of novel, previously unknown IRF4 interactors in the Th17/Treg context, such as RORγt, AHR, IRF8, BACH2, SATB1, and FLI1. Moreover, our data reveal that most of these transcription factors are recruited to IRF composite elements for the regulation of cell type-specific transcriptional programs providing a valuable resource for studying IRF4-mediated gene regulatory programs in pro- and anti-inflammatory immune responses.
Publisher
Cold Spring Harbor Laboratory