Opposing chromatin remodelers control transcription initiation frequency and start site selection
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Abstract
Precise nucleosome organization at eukaryotic promoters is thought to be generated by multiple chromatin remodeler (CR) enzymes and to affect transcription initiation. Using an integrated analysis of chromatin remodeler binding and nucleosome occupancy following rapid remodeler depletion, we investigated the interplay between these enzymes and their impact on transcription in yeast. We show that many promoters are affected by multiple CRs that operate in concert or in opposition to position the key transcription start site (TSS)-associated +1 nucleosome. We also show that nucleosome movement after CR inactivation usually results from the activity of another CR and that in the absence of any remodeling activity, +1 nucleosomes largely maintain their positions. Finally, we present functional assays suggesting that +1 nucleosome positioning often reflects a trade-off between maximizing RNA polymerase recruitment and minimizing transcription initiation at incorrect sites. Our results provide a detailed picture of fundamental mechanisms linking promoter nucleosome architecture to transcription initiation.
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SWI/SNF localises to nucleosome-depleted regions (NDRs) in promoters and regulates the position of the transcription start site (TSS)-associated (or '+1') nucleosome critical for transcription initiation.
“SWI/SNF localises to nucleosome-depleted regions (NDRs) in promoters and regulates the position of the transcription start site (TSS)-associated (or ‘+1’) nucleosome critical for transcription initiation20.”
From SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes (2022) · cites this paper as [20]
Histone chaperones and ATP-dependent chromatin-remodelling complexes are important for gene regulation because they regulate nucleosome dynamics at promoters, restricting or increasing promoter accessibility for recruitment of transcription factors and RNA polymerase II (Pol II).
“Histone chaperones and ATP-dependent chromatin-remodelling complexes are accordingly important for gene regulation given they regulate nucleosome dynamics at promoters, restricting or increasing promoter accessibility for recruitment of transcription factors and RNA polymerase II (Pol II)19–23.”
From SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes (2022) · cites this paper as [20]
SWI/SNF modulates nucleosome position to regulate the expression of a subset of genes including stress-responsive genes.
“SWI/SNF modulates nucleosome position to regulate the expression of a subset of genes including stress-responsive genes20,37–40.”
From SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes (2022) · cites this paper as [20]
In the absence of Snf2, the +1 nucleosome is shifted towards the TATA-box at the PDR5 promoter.
“We utilised the published datasets of nucleosome occupancy20 and TSS49 and observed that in the absence of Snf2 the +1 nucleosome is shifted towards the TATA-box at the PDR5 promoter (Fig. 6a, red rectangle).”
From SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes (2022) · cites this paper as [20]
SWI/SNF regulates the expression of PDR5 by shifting the TSS-associated +1 nucleosome.
“Our results and a published report20 suggest that SWI/SNF regulates the expression of PDR5 by shifting the TSS-associated +1 nucleosome, which is critical for transcription initiation.”
From SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes (2022) · cites this paper as [20]
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References 79 · Cited by 126
- Authors
- Kubik, S., Bruzzone, M. J., Challal, D., Dreos, R., Mattarocci, S., Bucher, P., Libri, D., & Shore, D.
- Affiliations
- Institute of Genetics and Genomics in Geneva (CH)
- Centre National de la Recherche Scientifique (FR)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Shore, David
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2019-08
- Volume
- 26
- Issue
- 8
- Pages
- 744-754
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2966463765
- Cited by
- 126
- References
- 79
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 22 · 2023: 25 · 2022: 15 · 2021: 30 · 2020: 8 · 2019: 5
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Science Foundation
- Agence Nationale de la Recherche (ANR-11-LABX-0071, ANR-16-CE12-0022, ANR-11-IDEX-0005)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (170153)
- Université de Genève
- Canton de Genève
- Institute of Genetics and Genomics of Geneva
- 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
- chromatin remodelers, transcription initiation, transcription start site selection, nucleosome positioning, promoter architecture, Saccharomyces cerevisiae, RNA polymerase recruitment, nucleosome occupancy, chromatin remodeling
- MeSH terms
- DNA, Fungal, Micrococcal Nuclease, Nucleosomes, Saccharomyces cerevisiae, DNA, Intergenic, Transcription Initiation Site, Saccharomyces cerevisiae Proteins, Chromatin Assembly and Disassembly, Macromolecular Substances, Transcription Initiation, Genetic
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