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

Science. 2012 Nov 16;338(6109):975-80. doi: 10.1126/science.1228309. Epub 2012 Sep 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Cell Differentiation / genetics
  • Chromatin Immunoprecipitation
  • Humans
  • Immunomodulation / genetics*
  • Interferon Regulatory Factors / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Regulatory Elements, Transcriptional*
  • Th17 Cells / immunology*
  • Transcription Factor AP-1 / metabolism*
  • Transcriptional Activation*


  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • Interferon Regulatory Factors
  • Transcription Factor AP-1
  • interferon regulatory factor-4
  • interferon regulatory factor-8

Associated data

  • GEO/GSE40483