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

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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
Journal Title:
Genome Biology
Keywords:
Publication Date:
14 January 2021
Citation:
Chia, M., Li, C., Marques, S., Pelechano, V., Luscombe, N. M., & van Werven, F. J. (2021). High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts. Genome Biology, 22(1). doi:10.1186/s13059-020-02245-3
Abstract:
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 inSaccharomyces cerevisiaeto identify regulatory functions associated with transcribing alternative isoforms.ResultsCell-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.ConclusionsThe 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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001203 and FC001110), the UK Medical Research Council (FC001203 and FC001110), and the Wellcome Trust (FC001203 and FC001110), to FW and NL. MC is supported by an A*STAR scholarship. NL is also supported by a Wellcome Trust Investigator Award and core funding from the Okinawa Institute of Science & Technology. CL is funded by an EMBO long-term postdoctoral fellowship (ALTF 1499–2016). Minghao Chia is supported by an A*STAR scholarship.
Description:
ISSN:
1474-760X