The human V-preB promoter is a target for coordinated activation by early B cell factor and E47

J Immunol. 2002 May 15;168(10):5130-8. doi: 10.4049/jimmunol.168.10.5130.

Abstract

The development of mature B lymphoid cells involves a highly orchestrated regulation of stage- and lineage-specific genes. In this study, we report an analysis of the human surrogate L chain VpreB promoter. The promoter has an overall homology of 56% to the mouse counterpart and displays a preB cell-restricted activity in transient transfections in cell lines. The promoter harbors three independent binding sites for early B cell factor (EBF) as defined by EMSA and supershift experiments. These sites were important for the full function of the promoter in a preB cell line, and chromatin immunoprecipitation experiments indicate that EBF interacts with the promoter in vivo. In addition to this, ectopic expression of EBF induces the activity of a reporter gene under control of the VpreB promoter in epithelioid HeLa cells, an effect augmented by coexpression of the basic-helix-loop helix transcription factor E47. The ability to interact directly with E47 was shared by the promoters controlling the human mb-1 and B29 genes. These data indicate that the human VpreB promoter is a direct target for activation by EBF and E47 and that functional collaboration between these proteins may be of great importance in human B cell development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Line, Transformed
  • DNA-Binding Proteins / physiology*
  • Gene Rearrangement, B-Lymphocyte, Light Chain
  • HeLa Cells
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Immunoglobulin Light Chains
  • Immunoglobulin Light Chains, Surrogate
  • Immunoglobulin Variable Region / genetics*
  • Jurkat Cells
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic / immunology*
  • TCF Transcription Factors
  • Trans-Activators / physiology*
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors / physiology*

Substances

  • DNA-Binding Proteins
  • EBF1 protein, human
  • Ebf1 protein, mouse
  • Immunoglobulin Light Chains
  • Immunoglobulin Light Chains, Surrogate
  • Immunoglobulin Variable Region
  • Membrane Glycoproteins
  • TCF Transcription Factors
  • TCF7L1 protein, human
  • Tcf7l1 protein, mouse
  • Trans-Activators
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors