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

Author:

Glasmacher Elke1,Agrawal Smita1,Chang Abraham B.1,Murphy Theresa L.2,Zeng Wenwen1,Vander Lugt Bryan1,Khan Aly A.3,Ciofani Maria4,Spooner Chauncey J.1,Rutz Sascha1,Hackney Jason5,Nurieva Roza6,Escalante Carlos R.7,Ouyang Wenjun1,Littman Dan R.4,Murphy Kenneth M.2,Singh Harinder1

Affiliation:

1. Department of Discovery Immunology, Genentech, Incorporated, South San Francisco, CA 94080, USA.

2. Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.

3. Institute for Systems and Genomics Biology and Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA.

4. Skirball Institute of Biomolecular Medicine, Howard Hughes Medical Institute, New York University, New York, NY 10016, USA.

5. Department of Bioinformatics and Computational Biology, Genentech, Incorporated, South San Francisco, CA 94080, USA.

6. Department of Immunology, M. D. Anderson Cancer Center, Houston, TX 77054, USA.

7. Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA 23219, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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