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Genome-wide mapping of autonomous promoter activity in human cells
Open accessAbstract
Previous methods to systematically characterize sequence-intrinsic activity of promoters have been limited by relatively low throughput and the length of the sequences that could be tested. Here we present 'survey of regulatory elements' (SuRE), a method that assays more than 10 8 DNA fragments, each 0.2-2 kb in size, for their ability to drive transcription autonomously. In SuRE, a plasmid library of random genomic fragments upstream of a 20-bp barcode is constructed, and decoded by paired-end sequencing. This library is used to transfect cells, and barcodes in transcribed RNA are quantified by high-throughput sequencing. When applied to the human genome, we achieve 55-fold genome coverage, allowing us to map autonomous promoter activity genome-wide in K562 cells. By computational modeling we delineate subregions within promoters that are relevant for their activity. We show that antisense promoter transcription is generally dependent on the sense core promoter sequences, and that most enhancers and several families of repetitive elements act as autonomous transcription initiation sites.
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“In contrast with MPRAs relying on re-synthesis of candidate sequences, genome-wide ‘shotgun MPRAs’108,174,183,188 nicely avoid a priori assumptions about which sequences to test.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [188]
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Metadata
- Authors
- van Arensbergen, J., FitzPatrick, V. D., de Haas, M., Pagie, L., Sluimer, J., Bussemaker, H. J., & van Steensel, B.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Columbia University Irving Medical Center (US)
- Corresponding author
- van Arensbergen, Joris
- Bussemaker, Harmen J
- van Steensel, Bas
- Venue
- Nature Biotechnology
- Published
- 2016-12-26
- Volume
- 35
- Issue
- 2
- Pages
- 145-153
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC5498152
- OpenAlex
- W2566958422
- Cited by
- 140
- References
- 54
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 18 · 2023: 21 · 2022: 15 · 2021: 11 · 2020: 18 · 2019: 15 · 2018: 10 · 2017: 5
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1s10od021764-01)
- National Human Genome Research Institute (R01HG003008)
- National Institute of General Medical Sciences (T32GM008281, T32GM008798)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- transcription initiation, SURE, barcode sequencing, K562 cells, core promoter, enhancers, repetitive elements, genome-wide mapping
- MeSH terms
- Chromosome Mapping, DNA, Humans, Promoter Regions, Genetic, Transcriptional Activation, Gene Library, Genome, Human, Sequence Analysis, DNA, K562 Cells, Transcription Initiation, Genetic
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