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Dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by RNA polymerase II

Transcription-related proteins are frequently identified as targets of sumoylation, including multiple subunits of the RNA polymerase II (RNAPII) general transcription factors (GTFs). However, it is not known how sumoylation affects GTFs or whether they are sumoylated when they assemble at promoters...

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Autores principales: Baig, Mohammad S., Dou, Yimo, Bergey, Benjamin G., Bahar, Russell, Burgener, Justin M., Moallem, Marjan, McNeil, James B., Akhter, Akhi, Burke, Giovanni L., Sri Theivakadadcham, Veroni S., Richard, Patricia, D’Amours, Damien, Rosonina, Emanuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505008/
https://www.ncbi.nlm.nih.gov/pubmed/34587155
http://dx.doi.org/10.1371/journal.pgen.1009828
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author Baig, Mohammad S.
Dou, Yimo
Bergey, Benjamin G.
Bahar, Russell
Burgener, Justin M.
Moallem, Marjan
McNeil, James B.
Akhter, Akhi
Burke, Giovanni L.
Sri Theivakadadcham, Veroni S.
Richard, Patricia
D’Amours, Damien
Rosonina, Emanuel
author_facet Baig, Mohammad S.
Dou, Yimo
Bergey, Benjamin G.
Bahar, Russell
Burgener, Justin M.
Moallem, Marjan
McNeil, James B.
Akhter, Akhi
Burke, Giovanni L.
Sri Theivakadadcham, Veroni S.
Richard, Patricia
D’Amours, Damien
Rosonina, Emanuel
author_sort Baig, Mohammad S.
collection PubMed
description Transcription-related proteins are frequently identified as targets of sumoylation, including multiple subunits of the RNA polymerase II (RNAPII) general transcription factors (GTFs). However, it is not known how sumoylation affects GTFs or whether they are sumoylated when they assemble at promoters to facilitate RNAPII recruitment and transcription initiation. To explore how sumoylation can regulate transcription genome-wide, we performed SUMO ChIP-seq in yeast and found, in agreement with others, that most chromatin-associated sumoylated proteins are detected at genes encoding tRNAs and ribosomal proteins (RPGs). However, we also detected 147 robust SUMO peaks at promoters of non-ribosomal protein-coding genes (non-RPGs), indicating that sumoylation also regulates this gene class. Importantly, SUMO peaks at non-RPGs align specifically with binding sites of GTFs, but not other promoter-associated proteins, indicating that it is GTFs specifically that are sumoylated there. Predominantly, non-RPGs with SUMO peaks are among the most highly transcribed, have high levels of TFIIF, and show reduced RNAPII levels when cellular sumoylation is impaired, linking sumoylation with elevated transcription. However, detection of promoter-associated SUMO by ChIP might be limited to sites with high levels of substrate GTFs, and promoter-associated sumoylation at non-RPGs may actually be far more widespread than we detected. Among GTFs, we found that TFIIF is a major target of sumoylation, specifically at lysines 60/61 of its Tfg1 subunit, and elevating Tfg1 sumoylation resulted in decreased interaction of TFIIF with RNAPII. Interestingly, both reducing promoter-associated sumoylation, in a sumoylation-deficient Tfg1-K60/61R mutant strain, and elevating promoter-associated SUMO levels, by constitutively tethering SUMO to Tfg1, resulted in reduced RNAPII occupancy at non-RPGs. This implies that dynamic GTF sumoylation at non-RPG promoters, not simply the presence or absence of SUMO, is important for maintaining elevated transcription. Together, our findings reveal a novel mechanism of regulating the basal transcription machinery through sumoylation of promoter-bound GTFs.
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spelling pubmed-85050082021-10-12 Dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by RNA polymerase II Baig, Mohammad S. Dou, Yimo Bergey, Benjamin G. Bahar, Russell Burgener, Justin M. Moallem, Marjan McNeil, James B. Akhter, Akhi Burke, Giovanni L. Sri Theivakadadcham, Veroni S. Richard, Patricia D’Amours, Damien Rosonina, Emanuel PLoS Genet Research Article Transcription-related proteins are frequently identified as targets of sumoylation, including multiple subunits of the RNA polymerase II (RNAPII) general transcription factors (GTFs). However, it is not known how sumoylation affects GTFs or whether they are sumoylated when they assemble at promoters to facilitate RNAPII recruitment and transcription initiation. To explore how sumoylation can regulate transcription genome-wide, we performed SUMO ChIP-seq in yeast and found, in agreement with others, that most chromatin-associated sumoylated proteins are detected at genes encoding tRNAs and ribosomal proteins (RPGs). However, we also detected 147 robust SUMO peaks at promoters of non-ribosomal protein-coding genes (non-RPGs), indicating that sumoylation also regulates this gene class. Importantly, SUMO peaks at non-RPGs align specifically with binding sites of GTFs, but not other promoter-associated proteins, indicating that it is GTFs specifically that are sumoylated there. Predominantly, non-RPGs with SUMO peaks are among the most highly transcribed, have high levels of TFIIF, and show reduced RNAPII levels when cellular sumoylation is impaired, linking sumoylation with elevated transcription. However, detection of promoter-associated SUMO by ChIP might be limited to sites with high levels of substrate GTFs, and promoter-associated sumoylation at non-RPGs may actually be far more widespread than we detected. Among GTFs, we found that TFIIF is a major target of sumoylation, specifically at lysines 60/61 of its Tfg1 subunit, and elevating Tfg1 sumoylation resulted in decreased interaction of TFIIF with RNAPII. Interestingly, both reducing promoter-associated sumoylation, in a sumoylation-deficient Tfg1-K60/61R mutant strain, and elevating promoter-associated SUMO levels, by constitutively tethering SUMO to Tfg1, resulted in reduced RNAPII occupancy at non-RPGs. This implies that dynamic GTF sumoylation at non-RPG promoters, not simply the presence or absence of SUMO, is important for maintaining elevated transcription. Together, our findings reveal a novel mechanism of regulating the basal transcription machinery through sumoylation of promoter-bound GTFs. Public Library of Science 2021-09-29 /pmc/articles/PMC8505008/ /pubmed/34587155 http://dx.doi.org/10.1371/journal.pgen.1009828 Text en © 2021 Baig et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Baig, Mohammad S.
Dou, Yimo
Bergey, Benjamin G.
Bahar, Russell
Burgener, Justin M.
Moallem, Marjan
McNeil, James B.
Akhter, Akhi
Burke, Giovanni L.
Sri Theivakadadcham, Veroni S.
Richard, Patricia
D’Amours, Damien
Rosonina, Emanuel
Dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by RNA polymerase II
title Dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by RNA polymerase II
title_full Dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by RNA polymerase II
title_fullStr Dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by RNA polymerase II
title_full_unstemmed Dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by RNA polymerase II
title_short Dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by RNA polymerase II
title_sort dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by rna polymerase ii
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505008/
https://www.ncbi.nlm.nih.gov/pubmed/34587155
http://dx.doi.org/10.1371/journal.pgen.1009828
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