The disclosure provides methods of examining the binding of proteins to DNA across a genome (e.g., the entire genome or a portion thereof, such as one or more chromosomes or a chromosome regions). In particular, the disclosure relates to a method of identifying a regulatory region (e.g., a protein or enhancer region) of genomic DNA to which a protein of interest binds. In one aspect, the disclosure looks at tissue related regulation. In another aspect, the disclosure looks at developmental related regulation. In yet another aspect, the disclosure looks at regulation of expression in a particular disease state or disorder.