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

doi:10.1126/science.1228309

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

Immunology

Research output: Contribution to journal › Article › peer-review

262 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 (T_H17) 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_H17, B, and dendritic cell differentiation. IRF4 and BATF bind cooperatively to structurally divergent AICEs to promote gene activation and T_H17 differentiation. The AICE motif directs assembly of IRF4 or IRF8 with BATF heterodimers and is also used in T_H2, B, and dendritic cells. This genomic regulatory element and cognate factors appear to have evolved to integrate diverse immunomodulatory signals.

Original language	English (US)
Pages (from-to)	975-980
Number of pages	6
Journal	Science
Volume	338
Issue number	6109
DOIs	https://doi.org/10.1126/science.1228309
State	Published - Nov 16 2012

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Glasmacher, E., Agrawal, S., Chang, A. B., Murphy, T. L., Zeng, W., Lugt, B. V., Khan, A. A., Ciofani, M., Spooner, C. J., Rutz, S., Hackney, J., Nurieva, R., Escalante, C. R., Ouyang, W., Littman, D. R., Murphy, K. M., & 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, E, Agrawal, S, Chang, AB, Murphy, TL, Zeng, W, Lugt, BV, Khan, AA, Ciofani, M, Spooner, CJ, Rutz, S, Hackney, J, Nurieva, R, Escalante, CR, Ouyang, W, Littman, DR, Murphy, KM & Singh, H 2012, 'A genomic regulatory element that directs assembly and function of immune-specific AP-1 - IRF complexes', Science, vol. 338, no. 6109, pp. 975-980. https://doi.org/10.1126/science.1228309

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

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.",

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

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doi = "10.1126/science.1228309",

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AU - Zeng, Wenwen

AU - Lugt, Bryan Vander

AU - Khan, Aly A.

AU - Ciofani, Maria

AU - Spooner, Chauncey J.

AU - Rutz, Sascha

AU - Hackney, Jason

AU - Nurieva, Roza

AU - Escalante, Carlos R.

AU - Ouyang, Wenjun

AU - Littman, Dan R.

AU - Murphy, Kenneth M.

AU - Singh, Harinder

PY - 2012/11/16

Y1 - 2012/11/16

N2 - 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.

AB - 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.

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

Abstract

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MD Anderson CCSG core facilities

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