Evidence map›Paper›PMID 35678392›Full record

ArticleeLife2022

Dynamic spreading of chromatin-mediated gene silencing and reactivation between neighboring genes in single cells.

Sarah Lensch, Michael H Herschl, Connor H Ludwig, Joydeb Sinha, Michaela M Hinks, Adi Mukund, Taihei Fujimori, Lacramioara Bintu

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
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

27 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review
  5. DNA topological regulation in RNA polymerase II transcription.Cellular & molecular biology letters · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
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 at 3 institutions in 2 countries.

Sarah LenschDepartment of Bioengineering, Stanford University, Stanford, United States.ORCID 0000-0003-1450-3242
Michael H HerschlUniversity of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, Berkeley, United States.
Connor H LudwigDepartment of Bioengineering, Stanford University, Stanford, United States.
Joydeb SinhaDepartment of Chemical and Systems Biology, Stanford University, Stanford, United States.
Michaela M HinksDepartment of Bioengineering, Stanford University, Stanford, United States.
Adi MukundBiophysics Program, Stanford University, Stanford, United States.ORCID 0000-0003-2752-1458
Taihei FujimoriDepartment of Bioengineering, Stanford University, Stanford, United States.
Lacramioara BintuDepartment of Bioengineering, Stanford University, Stanford, United States.ORCID 0000-0001-5443-6633
Bioengineering Center · RUStanford University · USUniversity of California, San Francisco · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
Graduate Training Program in BiotechnologyT32GM008412 · NIGMS · STANFORD UNIVERSITY · PI COCHRAN, JENNIFER R · 1991 to 2020
$5.5M
Single-cell analysis and synthetic control of mammalian chromatin dynamics and gene regulationR35GM128947 · NIGMS · STANFORD UNIVERSITY · PI Lacramioara Bintu · 2018 to 2026
$3.1M
Molecular Pharmacology Training GrantT32GM113854 · NIGMS · STANFORD UNIVERSITY · PI MOCHLY-ROSEN, DARIA · 2015 to 2019
$1.1M
NIGMS NIH HHS R35 GM128947NIGMS NIH HHS T32 GM007365NIGMS NIH HHS T32 GM008412NIGMS NIH HHS T32 GM113854
6 · The paper itself

Abstract

In mammalian cells genes that are in close proximity can be transcriptionally coupled: silencing or activating one gene can affect its neighbors. Understanding these dynamics is important for natural processes, such as heterochromatin spreading during development and aging, and when designing synthetic gene regulation circuits. Here, we systematically dissect this process in single cells by recruiting and releasing repressive chromatin regulators at dual-gene synthetic reporters, and measuring how fast gene silencing and reactivation spread as a function of intergenic distance and configuration of insulator elements. We find that silencing by KRAB, associated with histone methylation, spreads between two genes within hours, with a time delay that increases with distance. This fast KRAB-mediated spreading is not blocked by the classical cHS4 insulators. Silencing by histone deacetylase HDAC4 of the upstream gene can also facilitate background silencing of the downstream gene by PRC2, but with a days-long delay that does not change with distance. This slower silencing can sometimes be stopped by insulators. Gene reactivation of neighboring genes is also coupled, with strong promoters and insulators determining the order of reactivation. Our data can be described by a model of multi-gene regulation that builds upon previous knowledge of heterochromatin spreading, where both gene silencing and gene reactivation can act at a distance, allowing for coordinated dynamics via chromatin regulator recruitment.

Indexed as

ChromatinHeterochromatinAnimalsGene Expression RegulationGene SilencingInsulator ElementsMammalsChromatinHeterochromatinchromatin regulationchromosomesepigeneticsgene expressionhumaninsulatorsmammalian synthetic biologyspatial-temporal dynamics

Identifiers

PMID35678392
PMCPMC9183234
OpenAlexW4281696950

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.