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Shao-Shan Carol Huang, Special Seminar
April 25, 2016 @ 11:00 am - 12:00 pm
Shao-Shan Carol Huang, Ph.D.
“Efficient mapping of genome-wide regulatory elements for biological insights”
We developed a high-throughput sequencing assay for rapid transcription factor binding site (TFBS) discovery, DNA affinity purification sequencing (DAP-seq), that uses in vitro prepared transcription factors (TFs) to capture native genomic DNA. We applied DAPseq to 1,812 Arabidopsis thaliana TFs to resolve motifs for 529 factors and genome-wide enrichment maps for 349 factors. Cumulatively, the ~2.7 million experimentally determined TFBSs captured the Arabidopsis cistrome and predicted thousands of TF target genes enriched for known and novel functions. Base-resolution epicistrome maps were established by comparison of TF-binding to genomic DNA with native cytosinemethylation patterns and genomic DNA that had been synthetically demethylated. This revealed methylcytosine inhibited binding of ~72% of factors and promoted binding of 4.3% of factors. Lastly, we showed DAP-seq binding sites provided a way to annotate genomic and epigenomic variations in natural populations and interpret results from genome-wide association studies. Overall, DAP-seq enables rapid development of base-resolution cistrome and epicistrome atlases for a wide-array of applications for eukaryotic genomes.