Massively parallel characterization of transcriptional regulatory elements
University of Washington · Sanofi (France) · +14 more institutions
Abstract
. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.7% of these sequences were active. By testing sequences in both orientations, we find promoters to have strand-orientation biases and their 200-nucleotide cores to function as non-cell-type-specific 'on switches' that provide similar expression levels to their associated gene. By contrast, enhancers have weaker…
Citation impact
- FWCI
- 48.68
- Percentile
- 100%
- References
- 78
Authors
17- VAVikram AgarwalCorresponding
University of Washington, Sanofi (France), Sanofi (United States)
- FIFumitaka Inoue
University of California, San Francisco, Kyoto University
- MSMax Schubach
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
- DPDmitry Penzar
Pirogov Russian National Research Medical University, Institute of Protein Research, Vavilov Institute of General Genetics
- BMBeth Martin
University of Washington
Topics & keywords
- Computational biology
- Enhancer
- Regulatory sequence
- Biology
- Cell type
- Genome
- Gene
- Genetics
Funding
- DFDeutsche ForschungsgemeinschaftAward: 464313370
- MOMinistry of Education, Culture, Sports, Science and Technology
- RSRussian Science FoundationAward: 20-74-10075
- NINational Institutes of HealthAwards: UM1HG009408, U24 HG009446, HG009446, 5T32HL007093
- NHNational Human Genome Research InstituteAwards: U24 HG009446, HG009446, UM1HG011966, UM1HG009408