We propose to use our high-throughput production facility for genome-wide identification of the chromosomal locations of regulatory elements in human and mouse cells. Sequence-specific and general transcription factors will be mapped across the genome using chromatin immunoprecipitation followed by DNA sequencing (ChlP-Seq). Long noncoding RNAs (IncRNAs) will be mapped using ChlRP-seq, a method by which specific chromatin-bound RNAs and their associated regions are isolated using oligonucleotides followed by sequencing of the precipitated DNA. The results obtained from our genome wide mapping experiments will greatly advance the efforts of the ENCODE consortium to comprehensively identify all functional elements in the human genome. Our experimental data will be subjected to stringent quality metrics already established by the consortium and the results made publicly available in a timely manner. Targeted biological validation experiments will be performed, along with integrative analyses. All experiments and analyses will be performed by a highly experienced and well-integrated team of experts that has already established a successful working relationship. We expect our center to contribute greatly to the annotation of the human and mouse genomes.

Public Health Relevance

A map of regulatory information is a valuable resource for understanding human biology and our genetic diversity. It is also valuable because a majority of single nucleotide polymorphisms that are associated with disease lie outside protein coding genes and are postulated to affect regulatory elements. Data from our project will be an important resource to help clinical scientists identify changes in regulatory regions that contribute to many human diseases.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
3U54HG006996-04S1
Application #
9319836
Study Section
Special Emphasis Panel (ZHG1-HGR-M (M1))
Program Officer
Feingold, Elise A
Project Start
2012-09-21
Project End
2017-07-31
Budget Start
2016-09-15
Budget End
2017-07-31
Support Year
4
Fiscal Year
2016
Total Cost
$1,320,614
Indirect Cost
$351,267
Name
Stanford University
Department
Genetics
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Guo, Yu; Perez, Andrew A; Hazelett, Dennis J et al. (2018) CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops. Genome Biol 19:160
Rhie, Suhn Kyong; Yao, Lijun; Luo, Zhifei et al. (2018) ZFX acts as a transcriptional activator in multiple types of human tumors by binding downstream of transcription start sites at the majority of CpG island promoters. Genome Res :
Liu, Yuwen; Yu, Shan; Dhiman, Vineet K et al. (2017) Functional assessment of human enhancer activities using whole-genome STARR-sequencing. Genome Biol 18:219
Ma, Lijia; Zhao, Boxuan; Chen, Kai et al. (2017) Evolution of transcript modification by N6-methyladenosine in primates. Genome Res 27:385-392
Araya, Carlos L; Cenik, Can; Reuter, Jason A et al. (2016) Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations. Nat Genet 48:117-25
Phanstiel, Douglas H; Boyle, Alan P; Heidari, Nastaran et al. (2015) Mango: a bias-correcting ChIA-PET analysis pipeline. Bioinformatics 31:3092-8
Melton, Collin; Reuter, Jason A; Spacek, Damek V et al. (2015) Recurrent somatic mutations in regulatory regions of human cancer genomes. Nat Genet 47:710-6
Yao, Lijing; Berman, Benjamin P; Farnham, Peggy J (2015) Demystifying the secret mission of enhancers: linking distal regulatory elements to target genes. Crit Rev Biochem Mol Biol 50:550-73
Grubert, Fabian; Zaugg, Judith B; Kasowski, Maya et al. (2015) Genetic Control of Chromatin States in Humans Involves Local and Distal Chromosomal Interactions. Cell 162:1051-65
Lay, Fides D; Liu, Yaping; Kelly, Theresa K et al. (2015) The role of DNA methylation in directing the functional organization of the cancer epigenome. Genome Res 25:467-77

Showing the most recent 10 out of 27 publications