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.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZHG1-HGR-M (M1))
Program Officer
Feingold, Elise A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Schools of Medicine
United States
Zip Code
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; Shen, Hui; Laird, Peter W et al. (2015) Inferring regulatory element landscapes and transcription factor networks from cancer methylomes. Genome Biol 16:105
Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W et al. (2015) Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans. Genome Res 25:1610-21
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
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
Phanstiel, Douglas H; Boyle, Alan P; Heidari, Nastaran et al. (2015) Mango: a bias-correcting ChIA-PET analysis pipeline. Bioinformatics 31:3092-8
Cheng, Yong; Ma, Zhihai; Kim, Bong-Hyun et al. (2014) Principles of regulatory information conservation between mouse and human. Nature 515:371-5
Boyle, Alan P; Araya, Carlos L; Brdlik, Cathleen et al. (2014) Comparative analysis of regulatory information and circuits across distant species. Nature 512:453-6
Kellis, Manolis; Wold, Barbara; Snyder, Michael P et al. (2014) Defining functional DNA elements in the human genome. Proc Natl Acad Sci U S A 111:6131-8

Showing the most recent 10 out of 21 publications