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Research in the ?eld of gene regulation is evolving rapidly in an ever-changing s- enti?c environment. Microarray techniques and comparative genomics have enabled more comprehensive studies of regulatory genomics and are proving to be powerful tools of discovery. The application of chromatin immunoprecipitation and microarrays (chIP-on-chip) to directly study the genomic binding locations of transcription factors has enabled more comprehensive modeling of regulatory networks. In addition, c- plete genome sequences and the comparison of numerous related species has dem- strated that conservation in non-coding DNA sequences often provides evidence for cis-regulatory binding sites. That said, much is still to be learned about the regulatory networks of these sequenced genomes. Systematic methods to decipher the regulatory mechanism are also crucial for c- roboratingthese regulatorynetworks.Thecoreof thesemethodsarethe motifdiscovery algorithms that can help predict cis-regulatory elements. These DNA-motif discovery programsarebecomingmoresophisticatedandare beginningto leverageevidencefrom comparative genomics (phylogenetic footprinting) and chIP-on-chip studies. How to use these new sources of evidence is an active area of research.