The plant corepressor TPL is recruited to diverse chromatin contexts, yet its mechanism of repression remains unclear. Previously, we leveraged the fact that TPL retains its function in a synthetic transcriptional circuit in the yeast model Saccharomyces cerevisiae to localize repressive function to two distinct domains. Here, we employed two unbiased whole-genome approaches to map the physical and genetic interactions of TPL at a repressed locus. We identified SPT4, SPT5, and SPT6 as necessary for repression with SPT4 acting as a bridge connecting TPL to SPT5 and SPT6. We discovered the association of multiple additional constituents of the transcriptional preinitiation complex at TPL-repressed promoters, specifically those involved early in transcription initiation. These findings were validated in yeast and plants, including a novel method to analyze the conditional loss of function of essential genes in plants. Our findings support a model where TPL nucleates preassembly of the transcription activation machinery to facilitate the rapid onset of transcription once repression is relieved.
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December 09 2024
A function of TPL/TBL1-type corepressors is to nucleate the assembly of the preinitiation complex
Alexander R. Leydon
,
Alexander R. Leydon
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Department of Biology,
University of Washington
, Seattle, WA, USA
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Benjamin Downing
,
Benjamin Downing
*
(Data curation, Formal analysis, Investigation, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Department of Biology,
University of Washington
, Seattle, WA, USA
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Janet Solano Sanchez
,
Janet Solano Sanchez
*
(Data curation, Formal analysis, Investigation, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Department of Biology,
University of Washington
, Seattle, WA, USA
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Raphael Loll-Krippleber
,
Raphael Loll-Krippleber
(Investigation, Writing - review & editing)
3Department of Biochemistry and Donnelly Centre,
University of Toronto
, Toronto, ON, USA
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Nathan M. Belliveau
,
Nathan M. Belliveau
(Investigation, Writing - review & editing)
1Department of Biology,
University of Washington
, Seattle, WA, USA
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Ricard A. Rodriguez-Mias
,
Ricard A. Rodriguez-Mias
(Formal analysis, Investigation, Writing - review & editing)
2Department of Genome Sciences,
University of Washington
, Seattle, WA, USA
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Andrew J. Bauer
,
Andrew J. Bauer
(Investigation, Writing - review & editing)
1Department of Biology,
University of Washington
, Seattle, WA, USA
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Isabella J. Watson
,
Isabella J. Watson
(Investigation, Writing - review & editing)
1Department of Biology,
University of Washington
, Seattle, WA, USA
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Lena Bae
,
Lena Bae
(Investigation, Writing - review & editing)
1Department of Biology,
University of Washington
, Seattle, WA, USA
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Judit Villén
,
Judit Villén
(Data curation, Funding acquisition, Resources, Supervision, Writing - review & editing)
2Department of Genome Sciences,
University of Washington
, Seattle, WA, USA
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Grant W. Brown
,
Grant W. Brown
(Funding acquisition, Writing - review & editing)
3Department of Biochemistry and Donnelly Centre,
University of Toronto
, Toronto, ON, USA
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Jennifer L. Nemhauser
(Conceptualization, Data curation, Funding acquisition, Methodology, Project administration, Resources, Supervision, Visualization, Writing - review & editing)
1Department of Biology,
University of Washington
, Seattle, WA, USA
Correspondence to Jennifer L. Nemhauser: [email protected]
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Alexander R. Leydon
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1Department of Biology,
University of Washington
, Seattle, WA, USA
Benjamin Downing
Data curation, Formal analysis, Investigation, Validation, Visualization, Writing - original draft, Writing - review & editing
*
1Department of Biology,
University of Washington
, Seattle, WA, USA
Janet Solano Sanchez
Data curation, Formal analysis, Investigation, Validation, Visualization, Writing - original draft, Writing - review & editing
*
1Department of Biology,
University of Washington
, Seattle, WA, USA
Raphael Loll-Krippleber
Investigation, Writing - review & editing
3Department of Biochemistry and Donnelly Centre,
University of Toronto
, Toronto, ON, USA
Nathan M. Belliveau
Investigation, Writing - review & editing
1Department of Biology,
University of Washington
, Seattle, WA, USA
Ricard A. Rodriguez-Mias
Formal analysis, Investigation, Writing - review & editing
2Department of Genome Sciences,
University of Washington
, Seattle, WA, USA
Andrew J. Bauer
Investigation, Writing - review & editing
1Department of Biology,
University of Washington
, Seattle, WA, USA
Isabella J. Watson
Investigation, Writing - review & editing
1Department of Biology,
University of Washington
, Seattle, WA, USA
Lena Bae
Investigation, Writing - review & editing
1Department of Biology,
University of Washington
, Seattle, WA, USA
Judit Villén
Data curation, Funding acquisition, Resources, Supervision, Writing - review & editing
2Department of Genome Sciences,
University of Washington
, Seattle, WA, USA
Grant W. Brown
Funding acquisition, Writing - review & editing
3Department of Biochemistry and Donnelly Centre,
University of Toronto
, Toronto, ON, USA
Correspondence to Jennifer L. Nemhauser: [email protected]
*
B. Downing and J. Solano Sanchez contributed equally to this paper.
Disclosures: The authors declare no competing interests exist.
Received:
April 24 2024
Revision Received:
September 04 2024
Accepted:
November 01 2024
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funder(s):
National Institutes of Health
- Award Id(s): R01-GM107084,R35-GM148135-01,5K99GM147355,R35-GM119536
Funder(s):
Howard Hughes Medical Institute
Funder(s):
Canadian Institutes of Health Research
- Award Id(s): FDN-159913
Funder(s):
Simons Foundation
Funder(s):
Life Sciences Research Foundation
© 2024 Leydon et al.
2024
Leydon et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
This work is licensed under a
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
.
J Cell Biol (2025) 224 (2): e202404103.
Article history
Received:
April 24 2024
Revision Received:
September 04 2024
Accepted:
November 01 2024
Citation
Alexander R. Leydon, Benjamin Downing, Janet Solano Sanchez, Raphael Loll-Krippleber, Nathan M. Belliveau, Ricard A. Rodriguez-Mias, Andrew J. Bauer, Isabella J. Watson, Lena Bae, Judit Villén, Grant W. Brown, Jennifer L. Nemhauser; A function of TPL/TBL1-type corepressors is to nucleate the assembly of the preinitiation complex. J Cell Biol 3 February 2025; 224 (2): e202404103. doi: https://doi.org/10.1083/jcb.202404103
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