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The Role of the Enhancer-Promoter Interactome in Determining Cell Identity
Chromatin Immunoprecipitation, coupled with sequencing, has shaped our understanding of how transcriptional machinery interacts with genomes to facilitate gene regulation. These protein-DNA interactions are fundamental components of primary-feature epigenetic signatures that are informative across development, gene regulation, and disease research. A challenge associated with these data is that they depict protein anchors in linear space and do not consider the complex and hierarchical genomic folding associated with DNA packaged in chromatin and further compacted into a nucleus. Here we combine chromatin immunoprecipitation with Hi-C in a single assay, known as HiChIP, to describe the interactome associated with protein anchors. By comparing the interactome of H3K27ac (enhancers), promoters (H3K4me3), and topological boundaries (CTCF) in iPSC and NSC, we can describe the different transcriptional landscape of the essential genes involved with pluripotency maintenance, NANOG and OCT4. We then investigate the enhancer interactome of NSC with regards to Alzheimer's polymorphisms identified through GWAS. We show four distinct enhancer regions associated with APOE, a highly implicated gene in Alzheimer's disease. These results posit that SNPs occurring at enhancer kilobases away from a gene promotor could impact gene regulation.  These data introduce an additional dimension to ChIP-seq experiments to more completely describe the mechanism of gene activation and provide a more robust annotation of both protein anchors to their target gene as well as disease-associated polymorphisms.

May 5, 2021 02:00 PM in London

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Cory Padilla
Head of Scientific Affairs @Dovetail Genomics
Cory received his Ph.D. from Georgia Institute of Technology in cellular and molecular biology and holds a B.S. from the University of California at Santa Cruz. Cory joined Dovetail Genomics in 2017 as part of the Research & Development team and now leads Scientific Affairs. Cory’s focus is to act as a liaison between the company and the scientific community. In this role, Cory identifies new research areas, captures feedback on customer needs for integration into product development and works to educate the community on advances and new products from Dovetail Genomics.