DNA-binding proteins control many essential cellular processes such as transcription, DNA repair, and DNA replication, to name a few. Identifying the DNA sequences that bind such proteins can provide considerable insight to these processes, however, methods for doing so are cumbersome and prone to artifacts. Now on page 424, van Steensel and Henikoff describe a new way of identifying DNA sequences that interact in vivo with specific proteins. They tethered the Escherichia coli Dam protein, which mediates adenine methylation, to GAL4, a well-studied DNA binding protein, and expressed the fusion in Drosophila. When the GAL4 binds to DNA, it brings Dam along, which leads to an increase of adenine methylation in the region—all in vivo. By monitoring the methylation of different genetic loci, it is possible to determine which ones are targets for GAL4 binding. Combining this approach with microarray technology could allow genome wide screens to find the target genes of DNA-binding proteins.