Project Summary This application is an administrative supplement request for 5UM1HG009436. The ENCODE project has produced high-resolution, high-quality maps of components of the `regulome' in a set of tissues and cell lines, identifying a collection of putative regulatory elements. Our proposal aims to generate and release data that test the functional relevance of these putative elements with high-throughput, pooled CRISPR screens, as well as a number of other methods that are aimed to understand the relationship between transcription factor levels, global accessibility at regulatory elements, an the effects on gene expression.