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The pTalpha promoter and enhancer are direct targets for transactivation by E box-binding proteins.

Publiceringsår: 2002
Språk: Engelska
Sidor: 911-920
Publikation/Tidskrift/Serie: Eur J Immunol
Volym: 32
Nummer: 3
Dokumenttyp: Artikel
Förlag: Wiley

Sammanfattning

The pre-Talpha (pTalpha?) gene encodes a protein that forms the pre-TCR together with the newly expressed TCR beta chain during a defined stage of early T cell development. The restricted expression of this gene has been suggested to depend on a promoter and an enhancer element containing E boxes, which are potential binding sites for basic helix-loop-helix (bHLH) proteins. We here report that increased expression of E47 and E12 mRNA in CD4(--)CD8(--)TCR(--) thymocytes correlates with the initiation of pTalpha? transcription. Furthermore, electrophoretic mobility shift assays suggested that E47 binds directly to both the pTalpha? promoter and enhancer in vitro. Ectopic expression of E47 in non-lymphoid HeLa cells resultedin a dose- and template-dependent activation of these control elements. In addition to this, ectopic expression of E47 in combination with the ets-protein Pu.1 and?/?or the Pu.1-interacting protein(Pip-1), resulted in a synergistic effect on the activity of the pTalpha? control elements. Thus, we suggest that E47, Pu.1 and Pip-1 are directly involved in the regulation of pTalpha expression inearly T cell development.

Disputation

Nyckelord

  • Biology and Life Sciences
  • Medicine and Health Sciences
  • Gene Expression Regulation : genetics
  • Hela Cells
  • Genes T-Cell Receptor alpha
  • Hamsters
  • Enhancer Elements (Genetics)
  • Electrophoretic Mobility Shift Assay
  • DNA-Binding Proteins/biosynthesis : genetics : physiology
  • Binding Sites
  • Animal
  • Promoter Regions (Genetics)
  • Protein Binding
  • Protein Precursors : genetics
  • Proto-Oncogene Proteins : genetics : physiology
  • RNA Messenger : genetics
  • Recombinant Fusion Proteins : genetics : metabolism
  • Regulatory Sequences Nucleic Acid
  • Trans-Activation (Genetics)
  • Trans-Activators : genetics : physiology
  • Transfection
  • Transcription Factors : physiology
  • Helix-Loop-Helix Motifs
  • Human
  • Mesocricetus
  • Mice
  • Mice Inbred C57BL

Övrigt

Published
Yes
  • ISSN: 0014-2980

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