Identification of Probabilistic Transcriptional Switches in the Ly49 Gene Cluster: A Eukaryotic Mechanism for Selective Gene Activation

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 the Ly49g gene functions as a mol...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2004-07, Vol.21 (1), p.55-66
Main Authors: Saleh, Ali, Davies, Gareth E., Pascal, Veronique, Wright, Paul W., Hodge, Deborah L., Cho, Edward H., Lockett, Stephen J., Abshari, Mehrnoosh, Anderson, Stephen K.
Format: Article
Language:English
Subjects:
Animals
Antigens, Ly - genetics
Binding sites
Carrier Proteins - metabolism
Gene expression
Gene Expression Regulation
Immune system
Killer Cells, Natural - physiology
Lasers
Lectins, C-Type
Mice
Multigene Family
NF-kappa B p50 Subunit
NK Cell Lectin-Like Receptor Subfamily A
Organophosphates - metabolism
Promoter Regions, Genetic
Proteins
Receptors, NK Cell Lectin-Like
RNA polymerase
Steroid Isomerases
Transcription Factors - metabolism
Transcriptional Activation
Transgenes
Viral infections
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Summary: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 the Ly49g gene 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 all Ly49 family members, and the relative strength of the forward promoter in each inhibitory Ly49 gene correlates with the percentage of natural killer cells that express a given receptor, supporting a promoter competition model of selective gene activation.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2004.06.005