Discovery and annotation of regulatory elements in metazoan genomes. (360G-Wellcome-083563_Z_07_Z)

Transcriptional regulatory elements -- both promoters and enhancers -- contain clusters of transcription factor binding sites. I propose a two-stage strategy for finding and annotating these elements. The first stage is to build a dictionary of transcription factor binding motifs (TFBMs). I have previously demonstrated that a novel motif inference tool (NestedMICA) can recover a significant fraction of fruitfly TFBMs. By refining this strategy and applying it to whole-genome datasets, I in tend to build comprehensive motif dictionaries for several key metazoan genomes. I also plan to find and annotate individual regulatory elements on a genome-wide scale. Since enhancers can occur far from the genes that they regulate, this will require new strategies for predicting these elements and -- where available -- integrating these predictions with functional genomics datasets such as ChIP/chip. The second part of this project will be to develop such tools to the point where they can be used to make good-quality regulatory annotation. The goal is to produce regulatory annotation of quality and utility comparable to the computational annotation of protein-coding genes by Ensembl.