Comparative Genomics of Transcription Factor Binding in Drosophila

Abstract

While the number of genome-wide, in vivo transcription factor binding datasets is growing, yielding greater insight into the role of regulatory DNA in development, evolution and disease, it is difficult to tease apart signal from noise and identify truly functional binding events. Comparative studies of transcription factor binding between closely related species offer one way to combat this problem, as functionally important aspects of enhancer architecture tend to be constrained by natural selection. Here we review the current field in the area of in vivo transcription factor binding in Drosophila, illustrating how evolutionary studies within the drosophilids are helping to unravel the complexity of the genomic regulatory code. A number of techniques exist for studying transcription factor binding on a genome-wide scale, including ChIP-chip, ChIP-seq and DamID; we touch on these and address the challenges and advantages of each with regard to working on non-model species. We also describe major findings in the field so far, focusing on comparative studies of the developmental regulatory network, the logic of combinatorial binding and the evolutionary properties of noncoding DNA. Finally, we examine how insights from Drosophila compare with similar studies in the vertebrates and address some open questions that have been raised by studies conducted thus far.