Transcription Factors and DNA Regulatory Elements

Abstract

The interactions between sequence‐specific transcription factors (TFs) and their DNA binding sites are an integral part of the gene regulatory networks within cells. My group developed highly parallel in vitro microarray technology, termed protein binding microarrays (PBMs), for the characterization of the sequence specificities of DNA‐protein interactions at high resolution. Using PBMs, we have determined the DNA binding specificities of hundreds of TFs from a wide range of species. More recently we have used the PBM technology to investigate TF heterodimers and higher order complexes. The PBM data have permitted us to identify novel TFs and their DNA binding sequence preferences, predict the target genes and condition‐specific regulatory roles of TFs, predict and analyze tissue‐specific transcriptional enhancers, investigate functional divergence of paralogous TFs within a TF family, investigate the molecular determinants of TF‐DNA recognition specificity, and distinguish direct versus indirect TF‐DNA interactions in vivo. Notably, not all DNA binding sites of a TF function equally. Further analyses of TFs and cis regulatory elements are likely to reveal features of cis regulatory sequences that are important in gene regulation.