TY - JOUR
T1 - A genomic regulatory element that directs assembly and function of immune-specific AP-1 - IRF complexes
AU - Glasmacher, Elke
AU - Agrawal, Smita
AU - Chang, Abraham B.
AU - Murphy, Theresa L.
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.
UR - http://www.scopus.com/inward/record.url?scp=84869116884&partnerID=8YFLogxK
U2 - 10.1126/science.1228309
DO - 10.1126/science.1228309
M3 - Article
C2 - 22983707
AN - SCOPUS:84869116884
SN - 0036-8075
VL - 338
SP - 975
EP - 980
JO - Science
JF - Science
IS - 6109
ER -