Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter

PLoS One. 2014 Sep 8;9(9):e106927. doi: 10.1371/journal.pone.0106927. eCollection 2014.

Abstract

Recombination activating gene-2 (RAG-2) and NWC are strongly evolutionarily conserved overlapping genes which are convergently transcribed. In non-lymphoid cells the NWC promoter is active whereas in lymphocytes it is inactive due to the DNA methylation. Analysing the mechanism responsible for lymphocyte-specific methylation and inactivation of NWC promoter we found that Ikaros, a lymphocyte-specific transcription factor, acts as a repressor of NWC promoter--thus identifying a new Ikaros target--but is insufficient for inducing its methylation which depends on the antisense transcription driven by RAG-2 promoter. Possible implications of these observations for understanding evolutionary mechanisms leading to lymphocyte specific expression of RAG genes are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Methylation
  • DNA Primers
  • DNA-Binding Proteins / physiology*
  • Down-Regulation
  • Electrophoretic Mobility Shift Assay
  • HEK293 Cells
  • Humans
  • Ikaros Transcription Factor / physiology*
  • Lymphocytes / immunology
  • Promoter Regions, Genetic*
  • Real-Time Polymerase Chain Reaction
  • Transcription, Genetic*

Substances

  • DNA Primers
  • DNA-Binding Proteins
  • IKZF1 protein, human
  • V(D)J recombination activating protein 2
  • Ikaros Transcription Factor

Grants and funding

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