Gene Regulation and Its Promoters and Enhancers
The proper development of a human from a single-cell embryo and the maintenance of its wellbeing—through dramatic changes in nutrition and environment—require exquisite regulation of our 20,000 genes. This regulation depends on both promoters, regions of DNA that reside close to the genes they regulate, and the interplay of promoters with enhancers, DNA sequences which can reside up to a million base pairs from the promoter. Because enhancers are often so far away from promoters, this has made it nearly impossible to predict their target genes and the effects on regulation.
John T. Lis, Molecular Biology and Genetics, and Haiyuan Yu, Biological Statistics and Computational Biology, are characterizing the regulatory effects of enhancer regions, to dissect out their molecular building blocks and to identify enhancer target genes. The team is using highly sensitive, high-resolution methods that detect changes in transcription genome-wide as well as CRISPR/Cas9 to create new cell lines with select mutations in order to determine the regulatory effects.
This research will lead to a better mechanistic and functional understanding of enhancers and will enable novel therapeutic targets for diseases such as cancer, where gene regulation is dysfunctional. NIH Award Number: 1UM1HG009393-01