The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells.
We utilized gene targeting by homologous recombination to define the role that MEF, a transcriptional activating member of the ETS family of transcription factors, plays in lymphopoiesis. MEF-/- mice have a profound reduction in the number of NK-T and NK cells. Purified MEF-/- NK cells cannot lyse tumor cell targets and secrete only minimal amounts of IFNgamma. Perforin protein expression is severely impaired in MEF-deficient NK cells, likely accounting for the lack of tumor cell cytotoxicity. Promoter studies and chromatin immunoprecipitation analyses demonstrate that MEF and not ETS-1 directly regulates transcription of the perforin gene in NK cells. Our results uncover a specific role of MEF in the development and function of NK cells and in innate immunity.
Lacorazza
H Daniel
HD
Laboratory of Molecular Aspects of Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Miyazaki
Yasushi
Y
Di Cristofano
Antonio
A
Deblasio
Anthony
A
Hedvat
Cyrus
C
Zhang
Jin
J
Cordon-Cardo
Carlos
C
Mao
Shifeng
S
Pandolfi
Pier Paolo
PP
Nimer
Stephen D
SD
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008214:Lymphocytes / Q000473:pathology; D038041:Lymphopoiesis; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011401:Promoter Regions, Genetic; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C491779:Elf4 protein, mouse; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014157:Transcription Factors; D054353:Perforin