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A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers
Open accessAbstract
While Mediator plays a key role in eukaryotic transcription, little is known about its mechanism of action. This study combines CRISPR-Cas9 genetic screens, degron assays, Hi-C, and cryoelectron microscopy (cryo-EM) to dissect the function and structure of mammalian Mediator (mMED). Deletion analyses in B, T, and embryonic stem cells (ESC) identified a core of essential subunits required for Pol II recruitment genome-wide. Conversely, loss of non-essential subunits mostly affects promoters linked to multiple enhancers. Contrary to current models, however, mMED and Pol II are dispensable to physically tether regulatory DNA, a topological activity requiring architectural proteins. Cryo-EM analysis revealed a conserved core, with non-essential subunits increasing structural complexity of the tail module, a primary transcription factor target. Changes in tail structure markedly increase Pol II and kinase module interactions. We propose that Mediator's structural pliability enables it to integrate and transmit regulatory signals and act as a functional, rather than an architectural bridge, between promoters and enhancers.
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“However, Promoter Capture Hi-C-based studies did not observe a significant change in enhancer–promoter contacts upon RNAP inhibition, including in cells rapidly depleted of cohesin or CTCF [349, 380].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [380]
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“However, it was shown recently that rapid removal of chromatin-bound Mediator and RNAP does not significantly affect chromosomal architecture, including enhancer–promoter interactions, in spite of triggering widespread transcriptional changes and cell cycle arrest [380].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [380]
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Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 46,047
Wickham, H. (2016) · Use R! · doi:10.1007/978-3-319-24277-4 · Cited by 34,873
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
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
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
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- Wickham, H. ggplot2: Elegant Graphics for Data Analysis, 2016, https://ggplot2-book.org/. · DOI
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Liquid–liquid phase separation drives cellular function and dysfunction in cancer
Mehta, S., & Zhang, J. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00444-7 · Cited by 464
Mechanisms of enhancer action: the known and the unknown
Panigrahi, A., & O’Malley, B. W. (2021) · Genome biology · doi:10.1186/s13059-021-02322-1 · Cited by 376
The relationship between genome structure and function
Oudelaar, A. M., & Higgs, D. R. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00303-x · Cited by 304
The Mediator complex as a master regulator of transcription by RNA polymerase II
Richter, W. F., Nayak, S., Iwasa, J., & Taatjes, D. J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00498-3 · Cited by 343
Metadata
- Authors
- El Khattabi, L., Zhao, H., Kalchschmidt, J., Young, N., Jung, S., Van Blerkom, P., Kieffer-Kwon, P., Kieffer-Kwon, K.-R., Park, S., Wang, X., Krebs, J., Tripathi, S., Sakabe, N., Sobreira, D. R., Huang, S.-C., Rao, S. S. P., Pruett, N., Chauss, D., Sadler, E., Lopez, A., Nóbrega, M. A., Aiden, E. L., Asturias, F. J., & Casellas, R.
- Affiliations
- University of Colorado Anschutz (US)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (US)
- University of Chicago (US)
- Baylor College of Medicine (US)
- National Institutes of Health (US)
- Corresponding author
- Asturias, Francisco J.
- Casellas, Rafael
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 178
- Issue
- 5
- Pages
- 1145-1158.e20
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7533040
- OpenAlex
- W2967977322
- Cited by
- 244
- References
- 102
- Citations by year
- 2026: 26 · 2025: 22 · 2024: 38 · 2023: 35 · 2022: 44 · 2021: 51 · 2020: 25 · 2019: 3
- FWCI
- 10.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- 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 › Nuclear Structure and Function
- Keywords
- Mediator complex, RNA polymerase II recruitment, enhancers, transcriptional regulation, Hi-C, cryo-electron microscopy
- MeSH terms
- Mouse Embryonic Stem Cells, Gene Editing, Cohesins, Animals, Cells, Cultured, Chromosomal Proteins, Non-Histone, Enhancer Elements, Genetic, Humans, Male, Mice, Inbred C57BL, Promoter Regions, Genetic, RNA Polymerase II, Saccharomyces cerevisiae, CD4-Positive T-Lymphocytes, Cell Cycle Proteins, Cryoelectron Microscopy, Protein Structure, Quaternary, Saccharomyces cerevisiae Proteins, Mice, Mediator Complex, CRISPR-Cas Systems
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