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

Published

Journal Article

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 (T(H)17) 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 T(H)17, B, and dendritic cell differentiation. IRF4 and BATF bind cooperatively to structurally divergent AICEs to promote gene activation and T(H)17 differentiation. The AICE motif directs assembly of IRF4 or IRF8 with BATF heterodimers and is also used in T(H)2, B, and dendritic cells. This genomic regulatory element and cognate factors appear to have evolved to integrate diverse immunomodulatory signals.

Full Text

Duke Authors

Cited Authors

  • Glasmacher, E; Agrawal, S; Chang, AB; Murphy, TL; Zeng, W; Vander Lugt, B; Khan, AA; Ciofani, M; Spooner, CJ; Rutz, S; Hackney, J; Nurieva, R; Escalante, CR; Ouyang, W; Littman, DR; Murphy, KM; Singh, H

Published Date

  • November 16, 2012

Published In

Volume / Issue

  • 338 / 6109

Start / End Page

  • 975 - 980

PubMed ID

  • 22983707

Pubmed Central ID

  • 22983707

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1228309

Language

  • eng

Conference Location

  • United States