A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes (P1322)

Autor: Elke Glasmacher, Smita Agrawal, Abraham Chang, Theresa Murphy, Wenwen Zeng, Bryan Vander Lugt, Aly Khan, Maria Ciofani, Chauncey Spooner, Sascha Rutz, Jason Hackney, Roza Nurieva, Carlos Escalante, Wenjun Ouyang, Dan Littman, Ken Murphy, Harinder Singh
Rok vydání: 2013
Předmět:
Zdroj: The Journal of Immunology. 190:208.6-208.6
ISSN: 1550-6606
0022-1767
Popis: 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.
Databáze: OpenAIRE