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 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.
Saleh
Ali
A
Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, National Cancer Institute-Frederick, MD 21702, USA.
Davies
Gareth E
GE
Pascal
Veronique
V
Wright
Paul W
PW
Hodge
Deborah L
DL
Cho
Edward H
EH
Lockett
Stephen J
SJ
Abshari
Mehrnoosh
M
Anderson
Stephen K
SK
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D002352:Carrier Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type; D051379:Mice; D005810:Multigene Family; D052002:NF-kappa B p50 Subunit; D055650:NK Cell Lectin-Like Receptor Subfamily A; D010755:Organophosphates / Q000378:metabolism; D011401:Promoter Regions, Genetic; D055630:Receptors, NK Cell Lectin-Like; D013251:Steroid Isomerases; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D019076:Transgenes
D000950:Antigens, Ly; D002352:Carrier Proteins; C527095:Klra7 protein, mouse; D037181:Lectins, C-Type; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D055650:NK Cell Lectin-Like Receptor Subfamily A; D010755:Organophosphates; D055630:Receptors, NK Cell Lectin-Like; D014157:Transcription Factors; C073701:Nfkb1 protein, mouse; C009524:tributyl phosphate; C490380:Ebp protein, mouse; D013251:Steroid Isomerases