Evidence map›Paper›PMID 40998810›Full record

ArticleNature communications2025

Super-silencers are crucial for development and carcinogenesis in B cells.

Di Huang, Hanna M Petrykowska, Dhaneshwar Kumar, Lela Kardava, Susan Moir, Behdad Afzali, Laura Elnitski, Ivan Ovcharenko

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Di HuangIntramural Research Program, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
Hanna M PetrykowskaTranslational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Dhaneshwar KumarImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Lela KardavaLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-9135-6026
Susan MoirLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0163-6911
Behdad AfzaliImmunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2968-1156
Laura ElnitskiTranslational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. elnitski@mail.nih.gov.ORCID http://orcid.org/0000-0003-1065-019X
Ivan OvcharenkoIntramural Research Program, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. ovcharen@nih.gov.ORCID http://orcid.org/0000-0002-9730-7732

Funding

Regulatory and epigenetic landscapes reveal biological processes, disease mechanisms and diagnostic markersZIAHG200323 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ELNITSKI, LAURA L · 2009 to 2025
$27.6M
Role of B Lymphocytes In HIV Infection And PathogenesisZIAAI000825 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MOIR, SUSAN · 2009 to 2025
$24.5M
Regulatory landscape of the human genome: comparative and evolutionary analysis.ZIALM200881 · NLM · NATIONAL LIBRARY OF MEDICINE · PI OVCHARENKO, IVAN · 2009 to 2025
$20.1M
Unravelling immunoregulatory circuits of tissue inflammationZIADK075149 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI AFZALI, BEHDAD · 2019 to 2025
$19.3M
Intramural NIH HHS ZIA AI000825Intramural NIH HHS ZIA DK075149Intramural NIH HHS ZIA HG200323Intramural NIH HHS ZIA LM200881U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1-ZIA-LM200881-12
6 · The paper itself

Abstract

The strength of the repressive histone H3K27me3 signal varies across silencers. Focusing on regions with unusually strong signals-super-silencers-we show that B-cell super-silencers are initially linked to gene upregulation in development, with target genes highly expressed in stem cells. About 13% of B-cell super-silencers convert to super-enhancers in B-cell lymphoma; 22% of these recur in over half of patients. Genes like BCL6 and BACH2 tied to these conversions are downregulated faster by JQ1, a super-enhancer-disrupting anti-cancer agent. Super-silencers are enriched for B-cell cancer-associated variants-both somatic and germline-and translocation breakpoints, exceeding levels in other regulatory elements like CTCF  binding sites. Over 80% of B-cell lymphoma t(3;14)(q27;q32) translocations fuse BCL6 super-silencers with enhancer-rich regions. Super-silencer repression depends on CpG content: CpG-rich elements block promoter-enhancer contacts; CpG-poor - inhibit looping. These findings highlight super-silencers' key role in B-cell regulation and suggest their alteration may be a primary factor of B-cell carcinogenesis.

Indexed as

B-LymphocytesCarcinogenesisLymphoma, B-CellAnimalsAzepinesBasic-Leucine Zipper Transcription FactorsCell Line, TumorCpG IslandsEnhancer Elements, GeneticGene Expression Regulation, NeoplasticHistonesHumansPromoter Regions, GeneticProto-Oncogene Proteins c-bcl-6Translocation, GeneticTriazolesAzepinesBasic-Leucine Zipper Transcription FactorsBCL6 protein, humanHistones(+)-JQ1 compoundProto-Oncogene Proteins c-bcl-6Triazoles

Identifiers

PMID40998810
PMCPMC12462470

What OpenQuestion holds

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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.