| abstract |
Methods for determining one or more biological effects of a compound on gene expression are described. These methods involve obtaining a nuclear extract from cells exposed to a compound and then combining the nuclear extract with a nucleic acid, or library of nucleic acids, containing one or more regulatory elements under conditions that allow formation of cis/trans complexes between the regulatory elements and components (e.g., DNA binding proteins) of the nuclear extract. The complexes so formed are then compared with complexes formed using nuclear extracts obtained the same but untreaed cells and the compound. Differences between the comlexes formed as a result of exposure of teh cells to the compound can then be assessed. The methods of th einvention are preferably carried out in a high throughput format, and are useful, for example, to assess efficacy, toxicity, and mechanism of action of a compound. Accordingly, the invention will be useful in developing new drugs, and in better understanding and improving compounds already in use or under development. |