Defining functional DNA elements in the human genome

Kellis, M., Wold, B., Snyder, M. P., Bernstein, B. E., Kundaje, A., Marinov, G. K., Ward, L. D., Birney, E., Crawford, G. E., Dekker, J., Dunham, I., Elnitski, L. L., Farnham, P. J., Feingold, E. A., Gerstein, M., Giddings, M. C., Gilbert, D. M., Gingeras, T. R., Green, E. D., Guigo, R., Hubbard, T., Kent, J., Lieb, J. D., Myers, R. M., Pazin, M. J., Ren, B., Stamatoyannopoulos, J. A., Weng, Z. P., White, K. P., Hardison, R. C. (April 2014) Defining functional DNA elements in the human genome. Proceedings of the National Academy of Sciences of the United States of America, 111 (17). pp. 6131-6138. ISSN 0027-8424

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URL: http://www.ncbi.nlm.nih.gov/pubmed/24753594
DOI: 10.1073/pnas.1318948111

Abstract

With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease.

Item Type: Paper
Uncontrolled Keywords: PARALLEL REPORTER ASSAY GENE-EXPRESSION CHROMATIN IMMUNOPRECIPITATION HUMAN-CELLS JUNK DNA SYSTEMATIC DISSECTION REGULATORY FUNCTIONS PURIFYING SELECTION ADAPTIVE EVOLUTION MAMMALIAN GENOME Multidisciplinary Sciences
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
Investigative techniques and equipment > assays > whole genome sequencing
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL labs > Gingeras lab
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Matt Covey
Date: April 2014
Date Deposited: 27 May 2014 15:55
Last Modified: 20 Dec 2017 21:27
PMCID: PMC4035993
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30182

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