Although our ability to determine the genome sequence of individuals is becoming facile, our understanding of the function of most of the human genome is limited. Mapping of regulatory information is particularly crucial since most (>85%) common variants associated with human disease lie outside of coding regions. Previous phases of ENCODE have made important contributions to the mapping of regulatory elements across the genome, but there is much more to be achieved, including the mapping of regulatory regions across many more tissues and at the resolution of individual cells as well as determining the exact regulators i.e. transcription factors that bind each region. In our Stanford ENCODE Production Center for Mapping of Regulatory Regions, we plan to use technologies that we have developed to map the binding sites for most transcription factors (TFs) in five major cell lines using chromatin immunoprecipitation of tagged TFs. We will further expand the catalog of regulatory elements by analyzing open chromatin regions in these cell lines and a wide variety of tissues and cell types from both normal and diseased human subjects consented for open access. Finally, we will map open chromatin regions and expression in single cells from these types of biosamples. These studies will greatly expand the catalog of regulatory regions in the human genome. The rapid deposition of data into the ENCODE Data Coordinating Center (DCC) will ensure quick public release. We expect the data and cell lines that are generated by this Center will be a valuable resource for the broad scientific community.
Much of human disease is due to changes in sequences that control gene expression. However, where these sequences lie in the vast sea of human DNA is not well known. This information is crucial for understanding human diseases and ultimately treating them. We plan to map regulatory regions in a large variety of tissues and cell types. This effort will reveal the exact regions bound by the majority of gene regulators, thereby establishing a ?Google Maps?-type view of regulatory regions encoded in the human genome.
| Mezger, Anja; Klemm, Sandy; Mann, Ishminder et al. (2018) High-throughput chromatin accessibility profiling at single-cell resolution. Nat Commun 9:3647 |
