Sequence reliance of a Drosophila context-dependent transcription factor

Despite binding similar cis elements in multiple locations, a single transcription factor often performs context-dependent functions at different loci. How factors integrate cis sequence and genomic context is still poorly understood and has implications for off-target effects in genetic engineering. The Drosophila context-dependent transcription factor CLAMP targets similar GA-rich cis elements on the X-chromosome and at the histone gene locus but recruits very different, loci-specific factors. We discover that CLAMP leverages information from both cis element and local sequence to perform context-specific functions. Our observations imply the importance of other cues, including protein-protein interactions and the presence of additional cofactors.