Genome-wide screens

Carpenter, A. E., and Sabatini, D.V. (2004) Systematic genome-wide screens of gene function Nat Rev Genet. 5, 11-22. 

The yeast PKC1 gene was originally identified in a genome-wide screen of S. cerevisiae using probes derived from cDNAs encoding isoenzymes of rat PKC (Levin et al., 1990). Yeast Pkclp has substrate specificity and primary sequence similar to some mammalian PKC isoforms (Levin et al., 1990 Watanabe et al., 1994). Since yeast Pkclp is similar to mammalian PKC, it was expected that DAG and Ca+ + would be involved in its activation. However, Pkclp purified from yeast does not respond to Ca++, DAG, phorbol esters, or phospholipids in vitro (Antonsson et al., 1994 Watanabe et al., 1994). Thus, the question as to whether Pkclp in yeast is activated by products of phospholipid hydrolysis remains to be answered. 

K. L. Fraser, A.G. Kamath, R.S. Ahringer, J. Plasterk, R.H. A genome-wide screen identifies 27 genes involved in transposon silencing in C. elegans. Curr. Biol. 2003,13 (15), 1311-1316. 

Lum, P. Y., Armour, C. D., Stepaniants, S. B., et al. (2004). Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes. Cell, 116, 121-137. 

To rapidly identify novel interactors, genome-wide screens for binding partners have been carried out in yeast and mammalian-based two-hybrid systems. As mentioned above, over 200 human NR cofactors have been identified. These interactors are important in the era of NR modulator discovery since each new cofactor carries the potential to recapitulate a particular cellular interaction and thus provides the basis for a molecular screen for molecules that uniquely affect the interaction. 

Carpenter A E, Sabatini D M (2004). Systematic genome-wide screens of gene fnnc-tion. Nature Rev. Genet. 5 11-22. 

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