TY - JOUR
T1 - The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells
AU - Lacorazza, H. Daniel
AU - Miyazaki, Yasushi
AU - Di Cristofano, Antonio
AU - Deblasio, Anthony
AU - Hedvat, Cyrus
AU - Zhang, Jin
AU - Cordon-Cardo, Carlos
AU - Mao, Shifeng
AU - Pandolfi, Pier Paolo
AU - Nimer, Stephen D.
N1 - Funding Information:
We thank the former manager of the Flow Cytometry Facility (MSKCC) Thomas Delohery for his assistance in cell sorting and cell cycle analysis, Dr. Vladimir Jankovic for his helpful suggestions on analyzing NK and CTL cell function, Dr. Janko Nikolich-Zugich for kindly providing the RMA-S and P815-Kb cell lines, and Dr. Isil Erel for technical assistance. This work was funded by NIH R01 DK52208 (S.D.N.), and a Norman and Rosita Winston Fellowship Award (Y.M.). P.P.P. is a Scholar of the Leukemia and Lymphoma Society.
PY - 2002/10/1
Y1 - 2002/10/1
N2 - 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 IFNγ. 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.
AB - 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 IFNγ. 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.
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U2 - 10.1016/S1074-7613(02)00422-3
DO - 10.1016/S1074-7613(02)00422-3
M3 - Article
C2 - 12387738
AN - SCOPUS:18644379642
SN - 1074-7613
VL - 17
SP - 437
EP - 449
JO - Immunity
JF - Immunity
IS - 4
ER -
