A large variety of proteins bind to specific parts of the genome to regulate 
gene expression, DNA replication, and chromatin structure. DamID is a powerful 
method used to map the genomic interaction sites of these proteins in vivo. It 
is based on fusing a protein of interest to Escherichia coli DNA adenine 
methyltransferase (dam). Expression of this fusion protein in vivo leads to 
preferential methylation of adenines in DNA surrounding the native binding sites 
of the dam fusion partner. Because adenine methylation does not occur 
endogenously in most eukaryotes, it provides a unique tag to mark protein 
interaction sites. The adenine-methylated DNA fragments are isolated by 
selective polymerase chain reaction amplification and can be identified by 
microarray hybridization. We and others have successfully applied DamID to the 
genome-wide identification of interaction sites of several transcription factors 
and other chromatin-associated proteins. This chapter discusses DamID technology 
in detail, and a step-by-step experimental protocol is provided for use in 
Drosophila cell lines.