A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte development

Cell. 1994 Jun 17;77(6):917-29. doi: 10.1016/0092-8674(94)90140-6.


During development of T lymphocytes, differential regulation of expression of the CD4 and CD8 glycoproteins is coupled to the choice of one of two pathways of differentiation. Thymocytes that express both of these coreceptors commit to either the helper lineage, shutting off CD8, or the cytotoxic lineage, shutting off CD4. We have used transgenic mice to identify an intronic regulatory region that controls CD4 gene expression during development. This region selectively extinguishes transgene expression in CD4-CD8+, but not CD4+CD8- nor CD4+CD8+ T cells. It also represses gene expression in CD4-CD8- immature thymocytes, indicating that the CD4 gene is derepressed during differentiation from the CD4-CD8- to the CD4+CD8+ stage. The negative element(s) is both orientation and position independent and acts also on heterologous regulatory sequences. Its properties are functionally similar to those of silencers described in yeast and in Drosophila, suggesting that we have identified a developmentally regulated vertebrate transcriptional silencer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • CD4 Antigens / biosynthesis
  • CD4 Antigens / genetics*
  • Cell Differentiation / genetics
  • Cell Line
  • DNA
  • Enhancer Elements, Genetic
  • Humans
  • Introns
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • RNA Splicing
  • Regulatory Sequences, Nucleic Acid*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • CD4 Antigens
  • DNA

Associated data

  • GENBANK/L30100