NWC, third evolutionarily conserved gene within RAG locus and its cell-type specific regulation

NWC is expressed at high level in all cells except mature lymphocytes and their RAG negative progenitors because in lymphocytes it is regulated by RAG-1 promoter while in other cells by its own, RAG-2 intragenic promoter. We found that lymphocyte specific inactivation of NWC promoter is caused by CpG island hypermethylation accompanied by site specific blocking of chromatin accessibility. However, the change of accessibility, in contrast to RAG promoters, is not accompanied by posttranslational modifications of histone H3 (met-K4 and acetyl-K9). These results indicate that accessibility of NWC promoter and RAG promoters is regulated by different epigenetic mechanisms. The model of epigenetic control of RAG/NWC locus is proposed and hypothesis on-the role of NWC transcription in regulation of RAG expression is presented.