Evidence map›Paper›PMID 40456162›Full record

ArticleBlood2025

Reactivation of developmentally silenced globin genes through forced linear recruitment of remote enhancers.

Anna-Karina Felder, Sjoerd J D Tjalsma, Han J M P Verhagen, Rezin Majied, Marjon J A M Verstegen, Thijs C J Verheul, Jeffrey van Haren, Rebecca Mohnani, Richard Gremmen, Peter H L Krijger and 3 more

Abstract read
In one paragraph

Article in Blood, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Expanding the CRISPR/Cas toolkit: applications in proteomics and theranostics.Frontiers in bioengineering and biotechnology · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Anna-Karina FelderOncode Institute, Utrecht, The Netherlands.ORCID 0000-0002-8895-9798
Sjoerd J D TjalsmaOncode Institute, Utrecht, The Netherlands.ORCID 0009-0005-3380-4894
Han J M P VerhagenSanquin Research Amsterdam and Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Rezin MajiedDepartment of Developmental Biology, Erasmus MC, Rotterdam, The Netherlands.ORCID 0000-0002-8224-1216
Marjon J A M VerstegenOncode Institute, Utrecht, The Netherlands.
Thijs C J VerheulDepartment of Developmental Biology, Erasmus MC, Rotterdam, The Netherlands.ORCID 0000-0001-5702-3420
Jeffrey van HarenDepartment of Developmental Biology, Erasmus MC, Rotterdam, The Netherlands.ORCID 0000-0002-3160-3547
Rebecca MohnaniOncode Institute, Utrecht, The Netherlands.ORCID 0009-0005-3387-6329
Richard GremmenOncode Institute, Utrecht, The Netherlands.ORCID 0009-0003-1494-8847
Peter H L KrijgerOncode Institute, Utrecht, The Netherlands.ORCID 0000-0003-1702-348X
Sjaak PhilipsenDepartment of Developmental Biology, Erasmus MC, Rotterdam, The Netherlands.ORCID 0000-0002-3690-1201
Emile van den AkkerSanquin Research Amsterdam and Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-2596-0046
Wouter de LaatOncode Institute, Utrecht, The Netherlands.ORCID 0000-0002-6393-595X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractThe human genome contains regulatory DNA elements, known as enhancers, that can activate gene transcription over long chromosomal distances. Here, we showed that enhancer distance can be critical for gene silencing. We demonstrated that linear recruitment of the normally distal strong HBB enhancer to developmentally silenced embryonic HBE or fetal HBG promoters through deletion or inversion of intervening DNA sequences led to strongly reactivated expression in adult erythroid cells and ex vivo differentiated hematopoietic stem and progenitor cells. A similar observation was made for the HBA locus in which deletion-to-recruit of the distal enhancer strongly reactivated embryonic HBZ expression. Overall, our work assigned function to seemingly nonregulatory genomic segments; by providing linear separation, they may support genes to autonomously control their transcriptional response to distal enhancers.

Indexed as

beta-GlobinsEnhancer Elements, GeneticGene Expression Regulation, DevelopmentalGene SilencingGlobinsAnimalsErythroid CellsFetal HemoglobinHematopoietic Stem CellsHumansMicePromoter Regions, Geneticbeta-GlobinsFetal HemoglobinGlobins

Identifiers

PMID40456162
PMCPMC12824704

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.