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PreprintCited by 2Genomics and Chromatin DynamicsNuclear Structure and FunctionChromatin Remodeling and Cancer

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Nucleosome Positioning Shapes Cryptic Antisense Transcription

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Kok, Jian Yi, Harvey, Zachary H., Axelsson, Elin, Berger, Frédéric·2025·PLoS Genetics
DOI 10.1101/2025.07.14.664753PMC PMC13075793

Preprint — published as 10.1371/journal.pgen.1012078

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Abstract

SUMMARY: Maintaining transcriptional fidelity is essential for precise gene regulation and genome stability. Despite this, cryptic antisense transcription, occurring opposite to canonical coding sequences, is a pervasive feature across all domains of life. How such potentially harmful cryptic sites are regulated remains incompletely understood. Here, we show that nucleosome arrays within gene bodies play a key role in suppressing cryptic transcription. Using the fission yeast Schizosaccharomyces pombe as a model, we demonstrate that CHD1-family chromatin remodelers coordinate with the transcription elongation machinery, specifically the PAF complex, to position nucleosomes at sites of cryptic transcription initiation within gene bodies. In the absence of CHD1, AT-rich sequences within gene bodies lose nucleosome occupancy, exposing promoter-like sequences that drive cryptic initiation. While cryptic transcription is generally detrimental, we identify a subset of antisense transcripts that encode critical meiotic genes, suggesting that cryptic transcription can also serve as a source of regulatory innovation. These findings underscore the essential role of nucleosome remodelers in maintaining transcriptional fidelity and reveal their broader contributions to cellular homeostasis and evolutionary adaptability.

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Metadata

Authors
Kok, J. Y., Harvey, Z. H., Axelsson, E., & Berger, F.
Affiliations
  • University of Vienna (AT)
  • Gregor Mendel Institute of Molecular Plant Biology (AT)
Corresponding author
Berger, Frédéric
ORCID
Venue
PLoS Genetics
Publisher
openRxiv
Published
2025-07-18
Volume
22
Issue
3
Pages
e1012078-e1012078
ISSN
1553-7390 (ISSN-L)
DOI
10.1101/2025.07.14.664753
PMC
PMC13075793
OpenAlex
W7135176058
Cited by
2
References
1
Citations by year
2026: 2
FWCI
4.13
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • European Molecular Biology Organization (ALTF169-2020)
  • Österreichischen Akademie der Wissenschaften
  • Austrian Science Fund (TAI 304, PAT6138924, PAT 1104523, ESP 213, P 32054, P36231)
  • Sungkyunkwan University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
nucleosome positioning, nucleosome remodeling, transcription elongation, gene body, transcriptional fidelity, AT-rich sequences, meiotic genes, Schizosaccharomyces pombe, transcriptional regulation
MeSH terms
Chromatin, Meiosis, Nucleosomes, Promoter Regions, Genetic, Schizosaccharomyces, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Fungal, RNA, Antisense, Schizosaccharomyces pombe Proteins, Chromatin Assembly and Disassembly, Genomic Instability

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