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Genome-scale chromatin interaction dynamic measurements for key components of the RNA Pol II general transcription machinery
BACKGROUND: A great deal of work has revealed in structural detail the components of the machinery responsible for mRNA gene transcription initiation. These include the general transcription factors (GTFs), which assemble at promoters along with RNA Polymerase II (Pol II) to form a preinitiation com...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402067/ https://www.ncbi.nlm.nih.gov/pubmed/37546819 http://dx.doi.org/10.1101/2023.07.25.550532 |
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author | Kupkova, Kristyna Shetty, Savera J. Hoffman, Elizabeth A. Bekiranov, Stefan Auble, David T. |
author_facet | Kupkova, Kristyna Shetty, Savera J. Hoffman, Elizabeth A. Bekiranov, Stefan Auble, David T. |
author_sort | Kupkova, Kristyna |
collection | PubMed |
description | BACKGROUND: A great deal of work has revealed in structural detail the components of the machinery responsible for mRNA gene transcription initiation. These include the general transcription factors (GTFs), which assemble at promoters along with RNA Polymerase II (Pol II) to form a preinitiation complex (PIC) aided by the activities of cofactors and site-specific transcription factors (TFs). However, less well understood are the in vivo PIC assembly pathways and their kinetics, an understanding of which is vital for determining on a mechanistic level how rates of in vivo RNA synthesis are established and how cofactors and TFs impact them. RESULTS: We used competition ChIP to obtain genome-scale estimates of the residence times for five GTFs: TBP, TFIIA, TFIIB, TFIIE and TFIIF in budding yeast. While many GTF-chromatin interactions were short-lived (< 1 min), there were numerous interactions with residence times in the several minutes range. Sets of genes with a shared function also shared similar patterns of GTF kinetic behavior. TFIIE, a GTF that enters the PIC late in the assembly process, had residence times correlated with RNA synthesis rates. CONCLUSIONS: The datasets and results reported here provide kinetic information for most of the Pol II-driven genes in this organism and therefore offer a rich resource for exploring the mechanistic relationships between PIC assembly, gene regulation, and transcription. The relationships between gene function and GTF dynamics suggest that shared sets of TFs tune PIC assembly kinetics to ensure appropriate levels of expression. |
format | Online Article Text |
id | pubmed-10402067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-104020672023-08-05 Genome-scale chromatin interaction dynamic measurements for key components of the RNA Pol II general transcription machinery Kupkova, Kristyna Shetty, Savera J. Hoffman, Elizabeth A. Bekiranov, Stefan Auble, David T. bioRxiv Article BACKGROUND: A great deal of work has revealed in structural detail the components of the machinery responsible for mRNA gene transcription initiation. These include the general transcription factors (GTFs), which assemble at promoters along with RNA Polymerase II (Pol II) to form a preinitiation complex (PIC) aided by the activities of cofactors and site-specific transcription factors (TFs). However, less well understood are the in vivo PIC assembly pathways and their kinetics, an understanding of which is vital for determining on a mechanistic level how rates of in vivo RNA synthesis are established and how cofactors and TFs impact them. RESULTS: We used competition ChIP to obtain genome-scale estimates of the residence times for five GTFs: TBP, TFIIA, TFIIB, TFIIE and TFIIF in budding yeast. While many GTF-chromatin interactions were short-lived (< 1 min), there were numerous interactions with residence times in the several minutes range. Sets of genes with a shared function also shared similar patterns of GTF kinetic behavior. TFIIE, a GTF that enters the PIC late in the assembly process, had residence times correlated with RNA synthesis rates. CONCLUSIONS: The datasets and results reported here provide kinetic information for most of the Pol II-driven genes in this organism and therefore offer a rich resource for exploring the mechanistic relationships between PIC assembly, gene regulation, and transcription. The relationships between gene function and GTF dynamics suggest that shared sets of TFs tune PIC assembly kinetics to ensure appropriate levels of expression. Cold Spring Harbor Laboratory 2023-07-26 /pmc/articles/PMC10402067/ /pubmed/37546819 http://dx.doi.org/10.1101/2023.07.25.550532 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Kupkova, Kristyna Shetty, Savera J. Hoffman, Elizabeth A. Bekiranov, Stefan Auble, David T. Genome-scale chromatin interaction dynamic measurements for key components of the RNA Pol II general transcription machinery |
title | Genome-scale chromatin interaction dynamic measurements for key components of the RNA Pol II general transcription machinery |
title_full | Genome-scale chromatin interaction dynamic measurements for key components of the RNA Pol II general transcription machinery |
title_fullStr | Genome-scale chromatin interaction dynamic measurements for key components of the RNA Pol II general transcription machinery |
title_full_unstemmed | Genome-scale chromatin interaction dynamic measurements for key components of the RNA Pol II general transcription machinery |
title_short | Genome-scale chromatin interaction dynamic measurements for key components of the RNA Pol II general transcription machinery |
title_sort | genome-scale chromatin interaction dynamic measurements for key components of the rna pol ii general transcription machinery |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402067/ https://www.ncbi.nlm.nih.gov/pubmed/37546819 http://dx.doi.org/10.1101/2023.07.25.550532 |
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