Abstract
NWC, newly discovered, evolutionarily conserved gene within recombination activating gene (RAG) locus is constitutively expressed in all cells except lymphocytes, in which it is developmentally regulated by RAG1 promoter. In lymphocytes, NWC promoter, which is located within RAG2 intron and drives expression of NWC in non-lymphocytes, is inactive. Here, a hypothesis on the role of transcription of NWC in lymphocyte-specific regulation of RAG expression and their suppression in all other cells is presented. It is proposed that during development, inactivation of NWC promoter and the placement of NWC under the control of RAG1 promoter releases RAG genes from permanent suppression and allows their lymphocyte specific expression but at the same time subjects them to transcriptional feedback inhibition type of suppression which could permit for a stringent control over their threat to genome stability and oncogenic potential.
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