Evidence map›Paper›PMID 42607687›Full record

ArticleCell genomics2026

Single-cell 3D genome imaging shows super-enhancer hubs are rare, nonspecific, and neither necessary nor sufficient for transcriptional bursting.

Derek J Le, Antonina Hafner, Achuthan Raja Venkatesh, Tee Udomlumleart, Sadhana Gaddam, Ana Novacic, Kevin C Wang, Alistair N Boettiger

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2026. 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
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0citing papers in PubMed
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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

8 authors.

Derek J LeDepartment of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Cancer Biology Program, Stanford University, Stanford, CA 94305, USA; Department of Dermatology, Stanford University, Stanford, CA 94305, USA.
Antonina HafnerDepartment of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Achuthan Raja VenkateshDepartment of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Biophysics Program, Stanford University, Stanford, CA 94305, USA.
Tee UdomlumleartDepartment of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Sadhana GaddamDepartment of Dermatology, Stanford University, Stanford, CA 94305, USA.
Ana NovacicDepartment of Genetics, Stanford University, Stanford, CA 94305, USA.
Kevin C WangCancer Biology Program, Stanford University, Stanford, CA 94305, USA; Department of Dermatology, Stanford University, Stanford, CA 94305, USA.
Alistair N BoettigerDepartment of Developmental Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: boettiger@stanford.edu.

Funding

Live-cell multiplex super-resolution imaging of chromatin state transitionsU01DK127419 · NIDDK · STANFORD UNIVERSITY · PI BINTU, LACRAMIOARA, BOETTIGER, ALISTAIR N. · 2020 to 2024
$5.3M
Mapping 3D-genome motion with next generation tracking technology to distinguish molecular drivers of cis-regulatory controlR01GM157292 · NIGMS · STANFORD UNIVERSITY · PI Alistair N. Boettiger · 2025 to 2026
$894k
NIDDK NIH HHS U01 DK127419NIGMS NIH HHS R01 GM157292
6 · The paper itself

Abstract

Super-enhancer (SE) hubs have been proposed to coordinate gene expression through 3D genome organization and transcriptional condensates. Using multiplexed imaging, we mapped hundreds of SEs in thousands of mouse embryonic stem cells and also paired SE position with nascent transcription measurements. We found that most SEs are spatially isolated, with multiway SE hubs occurring in only a small fraction of cells. Rare hubs were largely promiscuous, cooperative aggregates shaped by genomic proximity, nuclear speckle association, and general transcription machinery occupancy. Perturbing cohesin, CTCF, BET proteins, or RNA polymerase II showed that normal genome organization generally suppresses SE clustering. Combined RNA and DNA imaging demonstrated that SE hubs were neither necessary nor sufficient for transcriptional bursting, although larger hubs weakly increased burst probability. These results challenge models in which SE hubs are a dominant mechanism of enhancer function and instead suggest rare transcriptional crosstalk.

Indexed as

Enhancer Elements, GeneticGenomeImaging, Three-DimensionalSingle-Cell AnalysisSuper EnhancersTranscription, GeneticAnimalsCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsMiceMouse Embryonic Stem CellsRNA Polymerase IICell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsRNA Polymerase II3D genome organizationclusteringenhancer hubenhancersmultiplexed imagingsingle-cell gene expressionsuper-enhancers

Identifiers

PMID42607687
PMCPMC13689515

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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.