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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.

Ikaros and RAG-2-Mediated Antisense Transcription Are Responsible for Lymphocyte-Specific Inactivation of NWC Promoter