Evidence map›Paper›PMID 33453273›Full record

ArticleBiophysical journal2021

Differentiating cancer cells reveal early large-scale genome regulation by pericentric domains.

Jekabs Krigerts, Kristine Salmina, Talivaldis Freivalds, Pawel Zayakin, Felikss Rumnieks, Inna Inashkina, Alessandro Giuliani, Michael Hausmann, Jekaterina Erenpreisa

Open access · hybridAbstract read
In one paragraph

Article in Biophysical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. PeculiarGenes · 2024
    Article
  6. Review
  7. Article
  8. From Cell States to Cell Fates: Control of Cell State Transitions.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  9. Article
  10. Synchronization between Attractors: Genomic Mechanism of Cell-Fate Change.International journal of molecular sciences · 2023
    Review
  11. Spatial-Temporal Genome Regulation in Stress-Response and Cell-Fate Change.International journal of molecular sciences · 2023
    Review
  12. Article
  13. Article
  14. Review
  15. Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue.International journal of molecular sciences · 2022
    Review
  16. Review
  17. Article
  18. Article
  19. A Unified Genomic Mechanism of Cell-Fate Change.Results and problems in cell differentiation · 2022
    Article
  20. Review
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

9 authors at 3 institutions in 2 countries.

Jekabs KrigertsLatvian Biomedicine Research and Study Centre, Riga, Latvia; University of Latvia, Riga, Latvia.
Kristine SalminaLatvian Biomedicine Research and Study Centre, Riga, Latvia.
Talivaldis FreivaldsInstitute of Cardiology and Regenerative Medicine, University of Latvia, Riga, Latvia.
Pawel ZayakinLatvian Biomedicine Research and Study Centre, Riga, Latvia.
Felikss RumnieksLatvian Biomedicine Research and Study Centre, Riga, Latvia; University of Latvia, Riga, Latvia.
Inna InashkinaLatvian Biomedicine Research and Study Centre, Riga, Latvia.
Alessandro GiulianiEnvironment and Health Department, Italian National Institute of Health, Rome, Italy.
Michael HausmannKirchhoff Institute for Physics, Heidelberg University, Heidelberg, Germany. Electronic address: hausmann@kip.uni-heidelberg.de.
Jekaterina ErenpreisaLatvian Biomedicine Research and Study Centre, Riga, Latvia. Electronic address: katrina@biomed.lu.lv.
Latvian Biomedical Research and Study Centre · LVHeidelberg University · DEUniversity of Latvia · LV

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Finding out how cells prepare for fate change during differentiation commitment was our task. To address whether the constitutive pericentromere-associated domains (PADs) may be involved, we used a model system with known transcriptome data, MCF-7 breast cancer cells treated with the ErbB3 ligand heregulin (HRG), which induces differentiation and is used in the therapy of cancer. PAD-repressive heterochromatin (H3K9me3), centromere-associated-protein-specific, and active euchromatin (H3K4me3) antibodies, real-time PCR, acridine orange DNA structural test (AOT), and microscopic image analysis were applied. We found a two-step DNA unfolding after 15-20 and 60 min of HRG treatment, respectively. This behavior was consistent with biphasic activation of the early response genes (c-fos - fosL1/myc) and the timing of two transcriptome avalanches reported in the literature. In control, the average number of PADs negatively correlated with their size by scale-free distribution, and centromere clustering in turn correlated with PAD size, both indicating that PADs may create and modulate a suprachromosomal network by fusing and splitting a constant proportion of the constitutive heterochromatin. By 15 min of HRG treatment, the bursting unraveling of PADs from the nucleolus boundary occurred, coinciding with the first step of H3K4me3 chromatin unfolding, confirmed by AOT. The second step after 60 min of HRG treatment was associated with transcription of long noncoding RNA from PADs and peaking of fosL1/c-myc response. We hypothesize that the bursting of PAD clusters under a critical silencing threshold pushes the first transcription avalanche, whereas the destruction of the PAD network enables genome rewiring needed for differentiation repatterning, mediated by early response bivalent genes.

Indexed as

Breast NeoplasmsNeuregulin-1CentromereHeterochromatinHumansHeterochromatinNeuregulin-1

Identifiers

PMID33453273
PMCPMC7896032
OpenAlexW3120708703

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.