Identification of Probabilistic Transcriptional Switches in theLy49Gene Cluster: A Eukaryotic Mechanism for Selective Gene Activation

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Murine natural killer cells selectively express members of the Ly49 family of class I MHC receptors; however, the molecular mechanism controlling probabilistic expression of Ly49 proteins has not been defined. A pair of overlapping, divergent promoters discovered in theLy49ggene functions as a molecular switch that can produce a forward transcript containing the coding region of the gene (on position) or a noncoding transcript in the opposite direction (off position), and this element maintains transcription in the chosen direction. Competition of C/EBP and TBP transcription factors for overlapping binding sites determines the relative strength of the competing promoters and the probability of transcription in a given direction. Similar elements precede allLy49family members, and the relative strength of the forward promoter in each inhibitoryLy49gene correlates with the percentage of natural killer cells that express a given receptor, supporting a promoter competition model of selective gene activation.

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