This application is an administrative supplement request for 5UM1HG009436. The ENCODE project has produced high-resolution, high-quality maps of components of the `regulome' in a set of tissues and cell lines, identifying a collection of putative regulatory elements. Our proposal aims to generate and release data that test the functional relevance of these putative elements with high-throughput, pooled CRISPR screens, as well as a number of other methods that are aimed to understand the relationship between transcription factor levels, global accessibility at regulatory elements, an the effects on gene expression.

Public Health Relevance

This administrative supplement request will allow the generation and submission of large data sets that test putative functional elements with powerful, high-throughput gene editing and perturbation technologies coupled with high-throughput genome wide characterization of chromatin structure and gene expression, providing a validation as to the regulatory potential of these identified genomic elements.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
3UM1HG009436-04S1
Application #
10238366
Study Section
Program Officer
Pazin, Michael J
Project Start
2020-09-01
Project End
2022-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
4
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Stanford University
Department
Genetics
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Marinov, Georgi K; Kundaje, Anshul (2018) ChIP-ping the branches of the tree: functional genomics and the evolution of eukaryotic gene regulation. Brief Funct Genomics 17:116-137
Boyle, Evan A; Pritchard, Jonathan K; Greenleaf, William J (2018) High-resolution mapping of cancer cell networks using co-functional interactions. Mol Syst Biol 14:e8594
Boyle, Evan A; Andreasson, Johan O L; Chircus, Lauren M et al. (2017) High-throughput biochemical profiling reveals sequence determinants of dCas9 off-target binding and unbinding. Proc Natl Acad Sci U S A 114:5461-5466
Mumbach, Maxwell R; Satpathy, Ansuman T; Boyle, Evan A et al. (2017) Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements. Nat Genet 49:1602-1612
Corces, M Ryan; Trevino, Alexandro E; Hamilton, Emily G et al. (2017) An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat Methods 14:959-962
Schep, Alicia N; Wu, Beijing; Buenrostro, Jason D et al. (2017) chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data. Nat Methods 14:975-978