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

Publication ,  Journal Article
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 ...
Published in: Science
November 16, 2012

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.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

November 16, 2012

Volume

338

Issue

6109

Start / End Page

975 / 980

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factor AP-1
  • Th17 Cells
  • Regulatory Elements, Transcriptional
  • Mice, Inbred C57BL
  • Mice
  • Interferon Regulatory Factors
  • Immunomodulation
  • Humans
  • General Science & Technology
 

Citation

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Glasmacher, E., Agrawal, S., Chang, A. B., Murphy, T. L., Zeng, W., Vander Lugt, B., … Singh, H. (2012). A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science, 338(6109), 975–980. https://doi.org/10.1126/science.1228309
Glasmacher, Elke, Smita Agrawal, Abraham B. Chang, Theresa L. Murphy, Wenwen Zeng, Bryan Vander Lugt, Aly A. Khan, et al. “A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes.Science 338, no. 6109 (November 16, 2012): 975–80. https://doi.org/10.1126/science.1228309.
Glasmacher E, Agrawal S, Chang AB, Murphy TL, Zeng W, Vander Lugt B, et al. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science. 2012 Nov 16;338(6109):975–80.
Glasmacher, Elke, et al. “A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes.Science, vol. 338, no. 6109, Nov. 2012, pp. 975–80. Pubmed, doi:10.1126/science.1228309.
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. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science. 2012 Nov 16;338(6109):975–980.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

November 16, 2012

Volume

338

Issue

6109

Start / End Page

975 / 980

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factor AP-1
  • Th17 Cells
  • Regulatory Elements, Transcriptional
  • Mice, Inbred C57BL
  • Mice
  • Interferon Regulatory Factors
  • Immunomodulation
  • Humans
  • General Science & Technology