Transcription elongation can be sufficient, but is not necessary, to advance replication timing.
Overview
- Department of Biological Science, Florida State University, Tallahassee, FL 32306 USA
- San Diego Biomedical Research Institute, San Diego, CA 92121 USA
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN 55455 USA
- College of Medicine, Florida State University, Tallahassee, FL 32306 USA
- Division of Gene Regulation and Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands
Abstract
DNA replication timing (RT) often correlates with transcription during cell fate transitions, yet notable exceptions indicate a complex relationship. Using a reductionist system in mouse embryonic stem cells, we manipulate transcriptional length and strength at a single locus upstream of the silent, late-replicating Pleiotrophin (Ptn) gene. Small reporter genes driven by two of four promoters advance RT, whereas all promoters advance RT when driving the 96-kb endogenous Ptn gene. Inducible transcription of Ptn, but not the reporter, triggers a rapid and reversible RT advance, providing a system to manipulate RT independent of differentiation. Strikingly, deletion of the Ptn promoter and enhancers abolishes transcription yet does not prevent the developmental RT switch to early replication during neural differentiation. These findings, supported by parallel genome-wide analyses during differentiation, demonstrate that transcriptional elongation can causally advance RT in a rate-dependent and context-specific manner, but that transcription is neither necessary nor sufficient for RT advancement. Our results provide a solid empirical base with which to re-evaluate decades of seemingly contradictory literature.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data and to no code of its authors: see the Data section.
The paper's code and data availability statement is in the Data section.
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Data
Datasets cited
- geo:GSE310795, at NCBI GEO; found in “Data availability”
Other data links
- ebi.ac.uk/
biostudies/ , EMBL-EBI; found in the text, “Author contributions”sourcedata
Data availability
The datasets and computer code produced in this study are available in the following databases: Repli-Seq data: Gene Expression Omnibus GSE310795 (https://
The source data of this paper are collected in the following database record: biostudies:S-SCDT-10_103
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 9 keywords, 12 MeSH terms, 3 funders, 68 references.
Cite
This paper
Vouzas, A. E., Sasaki, T., Rivera-Mulia, J. C., Turner, J. L., Brown, A. N., Alexander, K. E., Brueckner, L., van Steensel, B., & Gilbert, D. M. (2026). Transcription elongation can be sufficient, but is not necessary, to advance replication timing. EMBO reports, 27(8), 1964-1999. https://
BibTeX
@article{vouzas2026trans
author = {Vouzas, Athanasios E and Sasaki, Takayo and Rivera-Mulia, Juan Carlos and Turner, Jesse L and Brown, Amber N and Alexander, Karen E and Brueckner, Laura and van Steensel, Bas and Gilbert, David M},
title = {{Transcription elongation can be sufficient, but is not necessary, to advance replication timing}},
journal = {EMBO reports},
year = {2026},
month = mar,
volume = {27},
number = {8},
pages = {1964--1999},
publisher = {Nature Publishing Group},
issn = {1469-221X},
doi = {10.1038/
url = {https://
pmid = {41876817},
pmcid = {PMC13121604}
}
RIS
TY - JOUR
AU - Vouzas, Athanasios E
AU - Sasaki, Takayo
AU - Rivera-Mulia, Juan Carlos
AU - Turner, Jesse L
AU - Brown, Amber N
AU - Alexander, Karen E
AU - Brueckner, Laura
AU - van Steensel, Bas
AU - Gilbert, David M
TI - Transcription elongation can be sufficient, but is not necessary, to advance replication timing
T2 - EMBO reports
J2 - EMBO Rep
PY - 2026
DA - 2026/
VL - 27
IS - 8
SP - 1964
EP - 1999
SN - 1469-221X
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
{
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"container-title": "EMBO reports",
"author": [
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