A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes.
basic_science · Level V
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- Record sourced from PubMed, PMID 22983707.
- Also identified by DOI 10.1126/science.1228309 and PMC identifier 5789805.
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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 (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.
Medical subject headings
- Animals
- Basic-Leucine Zipper Transcription Factors
- Basic-Leucine Zipper Transcription Factors/metabolism
- Cell Differentiation
- Cell Differentiation/genetics
- Chromatin Immunoprecipitation
- Humans
- Immunomodulation
- Immunomodulation/genetics
- Interferon Regulatory Factors
- Interferon Regulatory Factors/metabolism
- Mice
- Mice, Inbred C57BL
- Regulatory Elements, Transcriptional
- Th17 Cells
- Th17 Cells/immunology
- Transcription Factor AP-1
- Transcription Factor AP-1/metabolism
- Transcriptional Activation
- Interferon Regulatory Factor-8
- Interferon Regulatory Factor-4