Widespread Enhancer Activity from Core Promoters
Open accessAbstract
Gene expression in higher eukaryotes is precisely regulated in time and space through the interplay between promoters and gene-distal regulatory regions, known as enhancers. The original definition of enhancers implies the ability to activate gene expression remotely, while promoters entail the capability to locally induce gene expression. Despite the conventional distinction between them, promoters and enhancers share many genomic and epigenomic features. One intriguing finding in the gene regulation field comes from the observation that many core promoter regions display enhancer activity. Recent high-throughput reporter assays along with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-related approaches have indicated that this phenomenon is common and might have a strong impact on our global understanding of genome organisation and gene expression regulation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Promoters can have enhancer activity.
“Now, there is convincing evidence that promoters can have enhancer activity [72,73,74,75], while intragenic enhancers can act as alternative promoters [76].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [74]
Cites
Systematic Localization of Common Disease-Associated Variation in Regulatory DNA
Maurano, M. T., Humbert, R., Rynes, E., Thurman, R. E., Haugen, E., Wang, H., Reynolds, A. P., Sandstrom, R., Qu, H., Brody, J., et al. (2012) · Science · doi:10.1126/science.1222794 · Cited by 3,716 · see citing works
An atlas of active enhancers across human cell types and tissues
The FANTOM Consortium, Andersson, R., Gebhard, C., Miguel-Escalada, I., Hoof, I., Bornholdt, J., Boyd, M., Chen, Y., Zhao, X., Schmidl, C., et al. (2014) · Nature · doi:10.1038/nature12787 · Cited by 2,550 · see citing works
Histone modifications at human enhancers reflect global cell-type-specific gene expression
Heintzman, N. D., Hon, G. C., Hawkins, R. D., Kheradpour, P., Stark, A., Harp, L. F., Ye, Z., Lee, L. K., Stuart, R. K., Ching, C. W., et al. (2009) · Nature · doi:10.1038/nature07829 · Cited by 2,533 · see citing works
Widespread transcription at neuronal activity-regulated enhancers
Kim, T.-K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010) · Nature · doi:10.1038/nature09033 · Cited by 2,450 · see citing works
Combinatorial patterns of histone acetylations and methylations in the human genome
Wang, Z., Zang, C., Rosenfeld, J. A., Schones, D. E., Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Peng, W., Zhang, M. Q., et al. (2008) · Nature Genetics · doi:10.1038/ng.154 · Cited by 2,331 · see citing works
A unique chromatin signature uncovers early developmental enhancers in humans
Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., & Wysocka, J. (2011) · Nature · doi:10.1038/nature09692 · Cited by 2,233 · see citing works
The long-range interaction landscape of gene promoters
Sanyal, A., Lajoie, B. R., Jain, G., & Dekker, J. (2012) · Nature · doi:10.1038/nature11279 · Cited by 1,489 · see citing works
Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq
Arnold, C. D., Gerlach, D., Stelzer, C., Boryń, Ł. M., Rath, M., & Stark, A. (2013) · Science · doi:10.1126/science.1232542 · Cited by 1,125 · see citing works
Javierre, B. M., Burren, O. S., Wilder, S. P., Kreuzhuber, R., Hill, S. M., Sewitz, S., Cairns, J., Wingett, S. W., Várnai, C., Thiecke, M. J., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.037 · Cited by 1,046 · see citing works
A Large Fraction of Extragenic RNA Pol II Transcription Sites Overlap Enhancers
De Santa, F., Barozzi, I., Mietton, F., Ghisletti, S., Polletti, S., Tusi, B. K., Muller, H., Ragoussis, J., Wei, C.-L., & Natoli, G. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000384 · Cited by 934 · see citing works
BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis
Canver, M. C., Smith, E. C., Sher, F., Pinello, L., Sanjana, N. E., Shalem, O., Chen, D. D., Schupp, P. G., Vinjamur, D. S., Garcia, S. P., et al. (2015) · Nature · doi:10.1038/nature15521 · Cited by 886 · see citing works
Mumbach, M. R., Satpathy, A. T., Boyle, E. A., Dai, C., Gowen, B. G., Cho, S. W., Nguyen, M. L., Rubin, A. J., Granja, J. M., Kazane, K. R., et al. (2017) · Nature Genetics · doi:10.1038/ng.3963 · Cited by 490 · see citing works
Intragenic Enhancers Act as Alternative Promoters
Kowalczyk, M. S., Hughes, J. R., Garrick, D., Lynch, M. D., Sharpe, J. A., Sloane-Stanley, J. A., McGowan, S. J., De Gobbi, M., Hosseini, M., Vernimmen, D., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2011.12.021 · Cited by 267 · see citing works
Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions
Ernst, J., Melnikov, A., Zhang, X., Wang, L., Rogov, P., Mikkelsen, T. S., & Kellis, M. (2016) · Nature Biotechnology · doi:10.1038/nbt.3678 · Cited by 162 · see citing works
Wang, X., He, L., Goggin, S. M., Saadat, A., Wang, L., Sinnott-Armstrong, N., Claussnitzer, M., & Kellis, M. (2018) · Nature Communications · doi:10.1038/s41467-018-07746-1 · Cited by 159 · see citing works
Functional assessment of human enhancer activities using whole-genome STARR-sequencing
Liu, Y., Yu, S., Dhiman, V. K., Brunetti, T., Eckart, H., & White, K. P. (2017) · Genome Biology · doi:10.1186/s13059-017-1345-5 · Cited by 136 · see citing works
Andersson, R. (2015) · BioEssays · doi:10.1002/bies.201400162 · Cited by 127 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Fourth generation biofuel from genetically modified algal biomass: Challenges and future directions.
Shokravi, H., Shokravi, Z., Heidarrezaei, M., Ong, H. C., Rahimian Koloor, S. S., Petrů, M., Lau, W. J., & Ismail, A. F. (2021) · Chemosphere · doi:10.1016/j.chemosphere.2021.131535 · Cited by 127 · see citing works
Spindola, L. M., Santoro, M. L., Pan, P. M., Ota, V. K., Xavier, G., Carvalho, C. M., Talarico, F., Sleiman, P., March, M., Pellegrino, R., et al. (2019) · Clinical Epigenetics · doi:10.1186/s13148-019-0740-z · Cited by 25 · see citing works
Enhancer Function in the 3D Genome
Razin, S. V., Ulianov, S. V., & Iarovaia, O. V. (2023) · Genes · doi:10.3390/genes14061277 · Cited by 15 · see citing works
- Authors
- Medina-Rivera, A., Santiago-Algarra, D., Puthier, D., & Spicuglia, S.
- Affiliations
- Universidad Nacional Autónoma de México (MX)
- Inserm (FR)
- Corresponding author
- Spicuglia, Salvatore
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 43
- Issue
- 6
- Pages
- 452-468
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2801850745
- Cited by
- 78
- References
- 17
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 6 · 2021: 14 · 2020: 5 · 2019: 19 · 2018: 5 · 2017: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- green
- amu.hal.science
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Funders
- Inserm
- Aix-Marseille University
- ARC (PJA 20151203149)
- Plan Cancer (P036496)
- ‘Equipe Labellisée Ligue Contre le Cancer’
- CONACYT (269449)
- ‘Programa de Apoyo a Proyectos de investigación e innovación tecnológica’ – Universidad Nacional Autónoma de México (IA206517)
- SEP-CONACYT-ANUIES-ECOS-NORD (M17S02)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- enhancer activity, core promoter, enhancers, gene expression regulation, enhancer-promoter interactions, distal regulatory elements, epigenetic regulation, genome organization
- MeSH terms
- Animals, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Promoter Regions, Genetic, High-Throughput Screening Assays
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review