Evidence map›Paper›PMID 41280019›Full record

ArticlebioRxiv : the preprint server for biology2025

Reversing transgene silencing via targeted chromatin editing.

Sebastian Palacios, Elia Salibi, Eric Lu, Ron Weiss, Thorsten M Schlaeger, James J Collins, Domitilla Del Vecchio

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Sebastian PalaciosInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Elia SalibiDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.ORCID 0009-0003-8201-4237
Eric LuDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Ron WeissDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.ORCID 0000-0003-0396-2443
Thorsten M SchlaegerBoston Children's Hospital Stem Cell Program, Boston Children's Hospital, Boston, MA, 02115, USA.
James J CollinsInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Domitilla Del VecchioDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Funding

Synthetic Genetic Controller Circuits for Transcription Factor-Directed DifferentiationR56EB036090 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI DEL VECCHIO, DOMITILLA · 2024 to 2024
$600k
NIBIB NIH HHS R56 EB036090
6 · The paper itself

Abstract

Mammalian cell engineering offers the opportunity to uncover biological principles and develop next-generation biotechnologies. However, epigenetic silencing of transgenes hinders the control of gene expression in mammalian cells. Here, we use chromatin editing of an integrated reporter in CHO-K1 and human induced pluripotent stem cells to study the molecular interactions driving silencing and its reversal. After transient induction of either DNA methylation or H3K9me3, stable silencing was exclusively observed with both marks. Due to the positive feedback between DNA methylation and H3K9me3 and the relative low stability of H3K9me3, our model predicts that removing DNA methylation is sufficient for transgene reactivation. Accordingly, targeted DNA demethylation reactivated the reporter irrespective of whether silencing was achieved by inducing DNA methylation, H3K9me3, or by the endogenous cellular machinery. These results shed light on molecular mechanisms at play during silencing and provide engineering tools for potent and specific transgene reactivation in mammalian cells.

Indexed as

CHO-K1epigeneticsgenome engineeringhuman stem cellssynthetic biology

Identifiers

PMID41280019
PMCPMC12636370

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.