In the past year, the Cytotoxic Cell Studies group has made a major discovery that explains the phenomenon of selective gene activation. We have discovered a probabilistic transcriptional switch that controls Ly49 gene activation, and it appears that the separately evolved human KIR gene family uses the same type of switch, indicating that probabilistic switches will likely be involved in many systems where genes are selectively activated in a subset of the cells in a given tissue. This discovery has important implications for the control of stem cell differentiation, and may one day allow us to modify cell fate in differentiating systems such as bone marrow cultures.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010013-08
Application #
6950619
Study Section
(LEI)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2003
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Belanger, S; Tai, L-H; Anderson, S K et al. (2008) Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome. Genes Immun 9:509-21
Anderson, S K (2006) Transcriptional regulation of NK cell receptors. Curr Top Microbiol Immunol 298:59-75
Makrigiannis, A P; Patel, D; Goulet, M-L et al. (2005) Direct sequence comparison of two divergent class I MHC natural killer cell receptor haplotypes. Genes Immun 6:71-83
Anderson, S K; Dewar, K; Goulet, M-L et al. (2005) Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype. Genes Immun 6:481-92
Saleh, Ali; Davies, Gareth E; Pascal, Veronique et al. (2004) Identification of probabilistic transcriptional switches in the Ly49 gene cluster: a eukaryotic mechanism for selective gene activation. Immunity 21:55-66
Makrigiannis, Andrew P; Rousselle, Etienne; Anderson, Stephen K (2004) Independent control of Ly49g alleles: implications for NK cell repertoire selection and tumor cell killing. J Immunol 172:1414-25
Makrigiannis, Andrew P; Anderson, Stephen K (2003) Regulation of natural killer cell function. Cancer Biol Ther 2:610-6
Mason, Llewellyn H; Willette-Brown, Jami; Anderson, Stephen K et al. (2003) Receptor glycosylation regulates Ly-49 binding to MHC class I. J Immunol 171:4235-42
Gosselin, P; Makrigiannis, A P; Nalewaik, R et al. (2000) Characterization of the Ly49I promoter. Immunogenetics 51:326-31
Makrigiannis, A P; Anderson, S K (2000) Ly49 gene expression in different inbred mouse strains. Immunol Res 21:39-47

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