A Genomic Regulatory Element That Directs Assembly and Function of Immune-Specific AP-1–IRF Complexes

• DOI: 10.1126/science.1228309
• Publication Date: 2012-09-15T10:42:00Z
• Authors: 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
• Keywords: Transcriptional Activation; 0301 basic medicine; Chromatin Immunoprecipitation; Cell Differentiation; Immunomodulation; Mice, Inbred C57BL; Transcription Factor AP-1; Mice; 03 medical and health sciences; Basic-Leucine Zipper Transcription Factors; Interferon Regulatory Factors; Animals; Humans; Th17 Cells; Regulatory Elements, Transcriptional

Helping T Helper Transcription

Members of the interferon response family of transcription factors (IRFs) are specifically expressed in immune cells and are known to regulate their differentiation. IRF4 and IRF8 regulate gene expression by binding to other transcription factors, which results in their recruitment to composite motifs in the genome. Although the specific mechanism of how this regulation works in some immune cells is understood, how it occurs in T cells is not clear because the transcription factors that normally partner with IRFs are absent. Using genomic analysis,

Glasmacher et al.

(p. 975 , published online 13 September; see the Perspective by

Martinez and Rao

) now identify IRF4–AP-1 composite elements in T helper 17 (T H 17) cells and show that IRF4 and the AP-1 factor Batf cooperatively assemble on a large array of genes required for T H 17 cell differentiation and function. Assembly of such heterodimers was also observed in T H 2 cells, B cells, and dendritic cells, which suggests the general importance of this motif in immune cell differentiation.