Bidirectional activity of the NWC promoter is responsible for RAG-2 transcription in non-lymphoid cells

PLoS One. 2012;7(9):e44807. doi: 10.1371/journal.pone.0044807. Epub 2012 Sep 11.

Abstract

The recombination-activating genes (RAG-1 and RAG-2) encode a V(D)J recombinase responsible for rearrangements of antigen-receptor genes during T and B cell development, and RAG expression is known to correlate strictly with the process of rearrangement. In contrast to RAG-1, the expression of RAG-2 was not previously detected during any other stage of lymphopoiesis or in any other normal tissue. Here we report that the CpG island-associated promoter of the NWC gene (the third evolutionarily conserved gene in the RAG locus), which is located in the second intron of RAG-2, has bidirectional activity and is responsible for the detectable transcription of RAG-2 in some non-lymphoid tissues. We also identify evolutionarily conserved promoter fragments responsible for this bidirectional activity, and show that it is activated by transcription factor ZFP143. The possible implications of our findings are briefly discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • Conserved Sequence
  • CpG Islands
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation*
  • Genes, Reporter
  • Genome
  • HEK293 Cells
  • Humans
  • Introns
  • Mice
  • Models, Genetic
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Promoter Regions, Genetic*
  • Sequence Homology, Amino Acid
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • VDJ Recombinases / genetics*

Substances

  • DNA-Binding Proteins
  • Trans-Activators
  • Transcription Factors
  • V(D)J recombination activating protein 2
  • Zfp143 protein, mouse
  • VDJ Recombinases

Grants and funding

This work was supported by the Polish Ministry of Science and Higher Education (grant N N401 049138). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.