Identification and characterization of the murine Rag1 promoter

Mol Immunol. 1997 Aug-Sep;34(12-13):939-54. doi: 10.1016/s0161-5890(97)00000-x.

Abstract

Rag1 and Rag2 are required for the somatic rearrangement of immunoglobulin genes and T-cell receptor genes and the subsequent development of B and T cells. We describe the pattern of DNase I hypersensitive sites surrounding the Rag1 gene that accompanies mouse B-cell development and show that one of these sites corresponds to the murine Rag1 promoter. Transcription initiates over a 30 bp region, with approximately 70% of the transcripts initiating within a 5 bp region. The promoter contains neither a consensus TATA box nor an initiator, but does contain an AT rich sequence that could serve as a non-consensus TATA box. The Rag1 promoter directs only negligible levels of expression in transient transfection assays, but when combined with a heterologous enhancer, it is capable of driving significant levels of expression in pre-B cells, pre-T cells, and mature B cells. Methylation interference and mutation analysis reveal that the Rag1 promoter contains binding sites for E-box binding proteins, NF-Y proteins, and Ikaros proteins. These findings are discussed with respect to B-cell development and regulation of differential Rag expression by the promoter in pre-B, pre-T, and CNS cells.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chickens
  • Cloning, Molecular
  • DNA Footprinting
  • DNA-Binding Proteins / genetics*
  • Gene Rearrangement, B-Lymphocyte*
  • Gene Rearrangement, T-Lymphocyte*
  • Genes, RAG-1*
  • Goats
  • Homeodomain Proteins*
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Recombination, Genetic
  • Transcription, Genetic

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • RAG-1 protein

Associated data

  • GENBANK/AJ003151
  • GENBANK/U97668