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Transcriptional cofactors display specificity for distinct types of core promoters
Open accessAbstract
Transcriptional cofactors (COFs) communicate regulatory cues from enhancers to promoters and are central effectors of transcription activation and gene expression 1. Although some COFs have been shown to prefer certain promoter types 2-5 over others (for example, see refs 6,7), the extent to which different COFs display intrinsic specificities for distinct promoters is unclear. Here we use a high-throughput promoter-activity assay in Drosophila melanogaster S2 cells to screen 23 COFs for their ability to activate 72,000 candidate core promoters (CPs). We observe differential activation of CPs, indicating distinct regulatory preferences or 'compatibilities'8,9 between COFs and specific types of CPs. These functionally distinct CP types are differentially enriched for known sequence elements 2,4, such as the TATA box, downstream promoter element (DPE) or TCT motif, and display distinct chromatin properties at endogenous loci. Notably, the CP types differ in their relative abundance of H3K4me3 and H3K4me1 marks (see also refs 10-12), suggesting that these histone modifications might distinguish trans-regulatory factors rather than promoter- versus enhancer-type cis-regulatory elements. We confirm the existence of distinct COF-CP compatibilities in two additional Drosophila cell lines and in human cells, for which we find COFs that prefer TATA-box or CpG-island promoters, respectively. Distinct compatibilities between COFs and promoters can explain how different enhancers specifically activate distinct sets of genes 9, alternative promoters within the same genes, and distinct transcription start sites within the same promoter 13. Thus, COF-promoter compatibilities may underlie distinct transcriptional programs in species as divergent as flies and humans.
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“Enhancers regulating housekeeping genes may act via a distinct sets of TFs and cofactors than enhancers regulating developmentally specific genes79,120.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [120]
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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
Bioconductor: open software development for computational biology and bioinformatics
Gentleman, R. C., Carey, V. J., Bates, D. M., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004) · Genome biology · doi:10.1186/gb-2004-5-10-r80 · Cited by 12,082
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400
Heintzman, N. D., Stuart, R. K., Hon, G., Fu, Y., Ching, C. W., Hawkins, R. D., Barrera, L. O., Van Calcar, S., Qu, C., Ching, K. A., et al. (2007) · Nature Genetics · doi:10.1038/ng1966 · Cited by 3,398
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
Using GOstats to test gene lists for GO term association
Falcon, S., & Gentleman, R. C. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl567 · Cited by 2,019
A promoter-level mammalian expression atlas
The FANTOM Consortium and the RIKEN PMI and CLST (DGT) (2014) · Nature · doi:10.1038/nature13182 · Cited by 1,982
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Jullien, D., Guillou, E., Bernat-Fabre, S., Payet, A., Bourbon, H.-M. G., & Boube, M. (2022) · PLoS ONE · doi:10.1371/journal.pone.0275613 · Cited by 3
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Bergman, D. T., Jones, T., Liu, V., Siraj, L., Kang, H., Nasser, J., Kane, M., Nguyen, T. H., Grossman, S. R., Fulco, C. P., et al. (2021) · bioRxiv · doi:10.1101/2021.10.23.462170 · Cited by 5
Loubière, V., de Almeida, B. P., Pagani, M., & Stark, A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.10.561770 · Cited by 3
Self-citationMammalian enhancers and GWASs act proximally and seldom skip active genesPreprint
Narita, T., & Choudhary, C. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.29.625864 · Cited by 3
Zeng, X., Lee, H., Wang, C., Achikeh, P., Liu, C., & Hennighausen, L. G. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0425-x · Cited by 2
Hoppe, C., Bowles, J. R., Minchington, T. G., Sutcliffe, C., Upadhyai, P., Rattray, M., & Ashe, H. L. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/837179 · Cited by 2
Glaser, L. V., Steiger, M., Fuchs, A., van Bömmel, A., Einfeldt, E., Chung, H. R., Vingron, M., & Meijsing, S. H. (2021) · MDC Repository (Max-Delbrueck-Center for Molecular Medicine) · Cited by 2
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Majchrzycka, B., Mundlos, S., Krebs, A. R., & Ibrahim, D. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.14.682013 · Cited by 3
Taking a STAP at Core Promoter-Transcriptional Cofactor Specificity.
Siegenfeld, A. P., Lee, C., & Liau, B. B. (2019) · Biochemistry · doi:10.1021/acs.biochem.9b00537 · Cited by 1
How to build the regulatory genome: a constructionist guide to the cis-regulatory code
Bell, C. C., de Boer, C. G., Camellato, B. R., Delàs, M. J., Ibrahim, D. M., & Montgomery, M. T. (2026) · Development · doi:10.1242/dev.205516 · Cited by 2
The Role of CTCF-Mediated Chromatin Looping in Enhancer-Promoter Communication
Logie, C. (2024) · Springer eBooks · doi:10.1007/978-3-031-59286-7_16 · Cited by 1
High-resolution binding data of TFIID and cofactors show promoter-specific differences in vivoPreprint
Zeitlinger, J., Alcantara, S. G.-M., Bourdareau, S., & Weilert, M. (2025) · Research Square · doi:10.21203/rs.3.rs-8428476/v1 · Cited by 1
Lu, X. H., & Chen, X. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.24.059105
Sharrocks, A. D. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.738702238.793579142
Interpretable Prediction of mRNA Abundance from Promoter Sequence using Contextual Regression ModelsPreprint
Wang, S., & Wang, W. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.27.505543
Enhancers: Encoding Regulation Across Time
Easterwood, S., & Kim, T. H. (2022) · Cognitive systems monographs · doi:10.1007/978-3-031-17678-4_4
Subramanian, S., Thoms, J., Huang, Y., Cornejo, P., Koch, F. C., Jacquelin, S., Shen, S., Song, E., Joshi, S. M., Brownlee, C., et al. (2023) · bioRxiv · doi:10.1101/2023.04.18.537282
Characterization of core promoter activation by the Drosophila insulator-binding protein BEAFPreprint
Negedu, S., Vidrine, E. J., & Hart, C. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.25.661594
Additional file 1 of Mechanisms of enhancer action: the known and the unknown
Panigrahi, A., & O’Malley, B. W. (2021) · Figshare · doi:10.6084/m9.figshare.14429176
Nemčko, F., Sabath, K., Pagani, M., Kleinfercher, S., Plaschka, C., & Stark, A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.28.696747 · Cited by 1
Self-citationThe Core Promoter has an active role in interpreting patterning informationPreprint
Karmakar, S., Millen, K., & Bray, S. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.11.758330
Metadata
- Authors
- Haberle, V., Arnold, C. D., Pagani, M., Rath, M., Schernhuber, K., & Stark, A.
- Affiliations
- Research Institute of Molecular Pathology (AT)
- Corresponding author
- Stark, Alexander
- Venue
- Nature
- Published
- 2019-05-15
- Volume
- 570
- Issue
- 7759
- Pages
- 122-126
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7613045
- OpenAlex
- W2945999435
- Cited by
- 123
- References
- 53
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 20 · 2023: 20 · 2022: 25 · 2021: 22 · 2020: 18 · 2019: 8
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- 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
- transcriptional cofactors, core promoter, promoter specificity, enhancer-promoter interactions, transcriptional activation, H3K4me3, H3K4me1, histone modifications, TATA box, downstream promoter element, CpG islands, alternative promoters, transcription start sites, Drosophila melanogaster
- MeSH terms
- Animals, Cell Line, Chromatin, Drosophila melanogaster, Enhancer Elements, Genetic, Histones, Humans, Promoter Regions, Genetic, Substrate Specificity, Transcription Factors, Transcription, Genetic, Transcriptional Activation, TATA Box, CpG Islands, Transcription Initiation Site
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