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CCAAT-enhancer-binding proteins (C/EBP) regulate the tissue specific activity of the CD11c integrin gene promoter

C López-Rodríguez1, L Botella, A L Corbí

  • 1Hospital de la Princesa, c/Diego de León 62, 28006 Madrid, Spain.

The Journal of Biological Chemistry
|November 20, 1997
PubMed

Insights

CCAAT/enhancer-binding proteins (C/EBP) regulate CD11c/CD18 integrin expression in myeloid cells. These C/EBP factors interact with Sp1 to control gene activity, influencing cell adhesion and migration.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • CD11c/CD18 integrin is crucial for leukocyte functions like adhesion and migration.
  • Its expression on myeloid cells is transcriptionally regulated during differentiation.
  • CCAAT/enhancer-binding proteins (C/EBP) are known regulators of gene expression.

Purpose of the Study:

  • To investigate the role of C/EBP transcription factors in regulating the CD11c promoter activity.
  • To identify specific binding sites and interactions involved in CD11c gene regulation.
  • To understand the cell-type-specific mechanisms controlling CD11c/CD18 integrin expression.

Main Methods:

  • Analysis of the CD11c gene promoter activity using reporter assays.
  • Identification of C/EBP and Sp1 binding sites within the promoter region.
  • Electrophoretic mobility shift assays (EMSA) to study protein-DNA interactions.
  • Site-directed mutagenesis to disrupt specific binding sites.

Main Results:

  • C/EBP factors bind to the CEBP-80 site on the CD11c promoter.
  • Disruption of the CEBP-80 site decreased promoter activity in a cell-dependent manner.
  • C/EBPalpha transactivated the CD11c promoter, dependent on Sp1 binding sites.
  • A composite regulatory element (-90/-50) containing C/EBP, Sp1, and AP-1 sites showed differential enhancer activity.

Conclusions:

  • C/EBP factors are key regulators of basal, tissue-specific, and developmentally controlled CD11c/CD18 integrin expression.
  • Functional interactions between C/EBP and Sp1 factors modulate CD11c promoter activity.
  • A composite regulatory element dictates cell-type-specific expression of CD11c/CD18 integrin.

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