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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, Marcello F ; Lang, Stefan LU orcid ; Winkler, Thomas H ; Deinzer, Andrea ; Erber, Sebastian ; Nettelbeck, Dirk M ; Naschberger, Elisabeth ; Jochmann, Ramona ; Stürzl, Michael and Slany, Robert K , et al. (2013) In Molecular and Cellular Biology 33(7). p.44-1331
Abstract

CD83 is one of the best-known surface markers for fully mature dendritic cells (mature DCs), and its cell-type- and maturation-specific 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... (More)

CD83 is one of the best-known surface markers for fully mature dendritic cells (mature DCs), and its cell-type- and maturation-specific 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.

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publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Antigens, CD/genetics, Binding Sites, Dendritic Cells/metabolism, Enhancer Elements, Genetic/genetics, HEK293 Cells, HeLa Cells, Humans, Immunoglobulins/genetics, Interferon Regulatory Factors/genetics, Introns, Membrane Glycoproteins/genetics, Mice, NF-kappa B/genetics, NIH 3T3 Cells, Promoter Regions, Genetic/genetics, Transcription Factors/genetics, Transcriptional Activation/genetics
in
Molecular and Cellular Biology
volume
33
issue
7
pages
44 - 1331
publisher
American Society for Microbiology
external identifiers
  • pmid:23339870
  • scopus:84875241640
ISSN
0270-7306
DOI
10.1128/MCB.01051-12
language
English
LU publication?
no
id
74f4b086-7d5a-4ef9-bde4-159a66904b8a
date added to LUP
2018-12-19 13:14:54
date last changed
2024-04-15 19:36:56
@article{74f4b086-7d5a-4ef9-bde4-159a66904b8a,
  abstract     = {{<p>CD83 is one of the best-known surface markers for fully mature dendritic cells (mature DCs), and its cell-type- and maturation-specific 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.</p>}},
  author       = {{Stein, Marcello F and Lang, Stefan and Winkler, Thomas H and Deinzer, Andrea and Erber, Sebastian and Nettelbeck, Dirk M and Naschberger, Elisabeth and Jochmann, Ramona and Stürzl, Michael and Slany, Robert K and Werner, Thomas and Steinkasserer, Alexander and Knippertz, Ilka}},
  issn         = {{0270-7306}},
  keywords     = {{Animals; Antigens, CD/genetics; Binding Sites; Dendritic Cells/metabolism; Enhancer Elements, Genetic/genetics; HEK293 Cells; HeLa Cells; Humans; Immunoglobulins/genetics; Interferon Regulatory Factors/genetics; Introns; Membrane Glycoproteins/genetics; Mice; NF-kappa B/genetics; NIH 3T3 Cells; Promoter Regions, Genetic/genetics; Transcription Factors/genetics; Transcriptional Activation/genetics}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{44--1331}},
  publisher    = {{American Society for Microbiology}},
  series       = {{Molecular and Cellular Biology}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1128/MCB.01051-12}},
  doi          = {{10.1128/MCB.01051-12}},
  volume       = {{33}},
  year         = {{2013}},
}