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High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts

BACKGROUND: The start and end sites of messenger RNAs (TSSs and TESs) are highly regulated, often in a cell-type-specific manner. Yet the contribution of transcript diversity in regulating gene expression remains largely elusive. We perform an integrative analysis of multiple highly synchronized cel...

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Autores principales: Chia, Minghao, Li, Cai, Marques, Sueli, Pelechano, Vicente, Luscombe, Nicholas M., van Werven, Folkert J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807719/
https://www.ncbi.nlm.nih.gov/pubmed/33446241
http://dx.doi.org/10.1186/s13059-020-02245-3
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author Chia, Minghao
Li, Cai
Marques, Sueli
Pelechano, Vicente
Luscombe, Nicholas M.
van Werven, Folkert J.
author_facet Chia, Minghao
Li, Cai
Marques, Sueli
Pelechano, Vicente
Luscombe, Nicholas M.
van Werven, Folkert J.
author_sort Chia, Minghao
collection PubMed
description BACKGROUND: The start and end sites of messenger RNAs (TSSs and TESs) are highly regulated, often in a cell-type-specific manner. Yet the contribution of transcript diversity in regulating gene expression remains largely elusive. We perform an integrative analysis of multiple highly synchronized cell-fate transitions and quantitative genomic techniques in Saccharomyces cerevisiae to identify regulatory functions associated with transcribing alternative isoforms. RESULTS: Cell-fate transitions feature widespread elevated expression of alternative TSS and, to a lesser degree, TES usage. These dynamically regulated alternative TSSs are located mostly upstream of canonical TSSs, but also within gene bodies possibly encoding for protein isoforms. Increased upstream alternative TSS usage is linked to various effects on canonical TSS levels, which range from co-activation to repression. We identified two key features linked to these outcomes: an interplay between alternative and canonical promoter strengths, and distance between alternative and canonical TSSs. These two regulatory properties give a plausible explanation of how locally transcribed alternative TSSs control gene transcription. Additionally, we find that specific chromatin modifiers Set2, Set3, and FACT play an important role in mediating gene repression via alternative TSSs, further supporting that the act of upstream transcription drives the local changes in gene transcription. CONCLUSIONS: The integrative analysis of multiple cell-fate transitions suggests the presence of a regulatory control system of alternative TSSs that is important for dynamic tuning of gene expression. Our work provides a framework for understanding how TSS heterogeneity governs eukaryotic gene expression, particularly during cell-fate changes.
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spelling pubmed-78077192021-01-15 High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts Chia, Minghao Li, Cai Marques, Sueli Pelechano, Vicente Luscombe, Nicholas M. van Werven, Folkert J. Genome Biol Research BACKGROUND: The start and end sites of messenger RNAs (TSSs and TESs) are highly regulated, often in a cell-type-specific manner. Yet the contribution of transcript diversity in regulating gene expression remains largely elusive. We perform an integrative analysis of multiple highly synchronized cell-fate transitions and quantitative genomic techniques in Saccharomyces cerevisiae to identify regulatory functions associated with transcribing alternative isoforms. RESULTS: Cell-fate transitions feature widespread elevated expression of alternative TSS and, to a lesser degree, TES usage. These dynamically regulated alternative TSSs are located mostly upstream of canonical TSSs, but also within gene bodies possibly encoding for protein isoforms. Increased upstream alternative TSS usage is linked to various effects on canonical TSS levels, which range from co-activation to repression. We identified two key features linked to these outcomes: an interplay between alternative and canonical promoter strengths, and distance between alternative and canonical TSSs. These two regulatory properties give a plausible explanation of how locally transcribed alternative TSSs control gene transcription. Additionally, we find that specific chromatin modifiers Set2, Set3, and FACT play an important role in mediating gene repression via alternative TSSs, further supporting that the act of upstream transcription drives the local changes in gene transcription. CONCLUSIONS: The integrative analysis of multiple cell-fate transitions suggests the presence of a regulatory control system of alternative TSSs that is important for dynamic tuning of gene expression. Our work provides a framework for understanding how TSS heterogeneity governs eukaryotic gene expression, particularly during cell-fate changes. BioMed Central 2021-01-14 /pmc/articles/PMC7807719/ /pubmed/33446241 http://dx.doi.org/10.1186/s13059-020-02245-3 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chia, Minghao
Li, Cai
Marques, Sueli
Pelechano, Vicente
Luscombe, Nicholas M.
van Werven, Folkert J.
High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts
title High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts
title_full High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts
title_fullStr High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts
title_full_unstemmed High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts
title_short High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts
title_sort high-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807719/
https://www.ncbi.nlm.nih.gov/pubmed/33446241
http://dx.doi.org/10.1186/s13059-020-02245-3
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