A genomic regulatory element that directs assembly and function of immune-specific AP-1 - IRF complexes

Elke Glasmacher, Smita Agrawal, Abraham B. Chang, Theresa L. Murphy, Wenwen Zeng, Bryan Vander Lugt, Aly A. Khan, Maria Ciofani, Chauncey J. Spooner, Sascha Rutz, Jason Hackney, Roza Nurieva, Carlos R. Escalante, Wenjun Ouyang, Dan R. Littman, Kenneth M. Murphy, Harinder Singh

Research output: Contribution to journalArticlepeer-review

236 Scopus citations

Abstract

Interferon regulatory factor 4 (IRF4) and IRF8 regulate B, T, macrophage, and dendritic cell differentiation. They are recruited to cis-regulatory Ets-IRF composite elements by PU.1 or Spi-B. How these IRFs target genes in most T cells is enigmatic given the absence of specific Ets partners. Chromatin immunoprecipitation sequencing in T helper 17 (TH17) cells reveals that IRF4 targets sequences enriched for activating protein 1 (AP-1)-IRF composite elements (AICEs) that are co-bound by BATF, an AP-1 factor required for TH17, B, and dendritic cell differentiation. IRF4 and BATF bind cooperatively to structurally divergent AICEs to promote gene activation and TH17 differentiation. The AICE motif directs assembly of IRF4 or IRF8 with BATF heterodimers and is also used in TH2, B, and dendritic cells. This genomic regulatory element and cognate factors appear to have evolved to integrate diverse immunomodulatory signals.

Original languageEnglish
Pages (from-to)975-980
Number of pages6
JournalScience
Volume338
Issue number6109
DOIs
StatePublished - Nov 16 2012

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