Multiple interferon regulatory factor and NF-κB sites cooperate in mediating cell-type-and maturation-specific activation of the human CD83 promoter in dendritic cells

Stein MF, Lang S, Winkler T, Deinzer A, Erber S, Nettelbeck DM, Naschberger E, Jochmann R, Stürzl M, Slany R, Werner T, Steinkasserer A, Knippertz I (2013)

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2013

Journal

Molecular and Cellular Biology American Society for Microbiology

Book Volume: 33

Pages Range: 1331-1344

Journal Issue: 7

DOI: 10.1128/MCB.01051-12

Abstract

CD83 is one of the best-known surface markers for fully mature dendritic cells (mature DCs), and its cell-type-and maturationspecific regulation makes the CD83 promoter an interesting tool for the genetic modulation of DCs. To determine the mechanisms regulating this DC-and maturation-specific CD83 expression, chromatin immunoprecipitation (ChIP)-on-chip microarray, biocomputational, reporter, electrophoretic mobility shift assay (EMSA), and ChIP analyses were performed. These studies led to the identification of a ternary transcriptional activation complex composed of an upstream regulatory element, a minimal promoter, and an enhancer, which have not been reported in this arrangement for any other gene so far. Notably, these DNA regions contain a complex framework of interferon regulatory factor (IRF)-and NF-κB transcription factor-binding sites mediating their arrangement. Mutation of any of the IRF-binding sites resulted in a significant loss of promoter activity, whereas overexpression of NF-κB transcription factors clearly enhanced transcription. We identified IRF-1, IRF-2, IRF-5, p50, p65, and cRel to be involved in regulating maturation-specific CD83 expression in DCs. Therefore, the characterization of this promoter complex not only contributes to the knowledge of DC-specific gene regulation but also suggests the involvement of a transcriptional module with binding sites separated into distinct regions in transcriptional activation as well as cell-type-and maturation-specific transcriptional targeting of DCs. © 2013, American Society for Microbiology.

Authors with CRIS profile

Thomas Winkler Professur für Genetik Anja Deinzer Institute of General Practice Elisabeth Naschberger Medizinische Fakultät Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie Robert Slany Lehrstuhl für Genetik Alexander Steinkasserer Professur für Experimentelle Dermatologie

Involved external institutions

Genomatix GmbH DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE)

How to cite

APA:

Stein, M.F., Lang, S., Winkler, T., Deinzer, A., Erber, S., Nettelbeck, D.M.,... Knippertz, I. (2013). Multiple interferon regulatory factor and NF-κB sites cooperate in mediating cell-type-and maturation-specific activation of the human CD83 promoter in dendritic cells. Molecular and Cellular Biology, 33(7), 1331-1344. https://dx.doi.org/10.1128/MCB.01051-12

MLA:

Stein, Marcello F., et al. "Multiple interferon regulatory factor and NF-κB sites cooperate in mediating cell-type-and maturation-specific activation of the human CD83 promoter in dendritic cells." Molecular and Cellular Biology 33.7 (2013): 1331-1344.

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