Evidence map›Paper›PMID 30531872›Full record

ArticleNature genetics2019

Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments.

Stephanie Fanucchi, Ezio T Fok, Emiliano Dalla, Youtaro Shibayama, Kathleen Börner, Erin Y Chang, Stoyan Stoychev, Maxim Imakaev, Dirk Grimm, Kevin C Wang and 3 more

Erratum issuedOpen access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Nature genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 173 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
173citing papers in PubMed, 2 pooled it
10.0field-weighted citation impact, top 1% 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

173 citing papers in PubMed, 2 syntheses or guidelines pooled it, 276 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Innate Immune Memory Responses in Organ Transplantation.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Direct roles of long non-coding RNAs in transcription activation.Nature structural & molecular biology · 2026
    Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review

113 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 9 institutions in 8 countries.

Stephanie FanucchiGene Expression and Biophysics Group, Division of Chemical, Systems and Synthetic Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Ezio T FokGene Expression and Biophysics Group, Division of Chemical, Systems and Synthetic Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Emiliano DallaGene Expression and Biophysics Group, Division of Chemical, Systems and Synthetic Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Youtaro ShibayamaGene Expression and Biophysics Group, Division of Chemical, Systems and Synthetic Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Kathleen BörnerDepartment of Infectious Diseases/Virology, BioQuant Center, Heidelberg University Hospital, Heidelberg, Germany.
Erin Y ChangDepartment of Dermatology, Stanford University, Stanford, CA, USA.
Stoyan StoychevBiomedical Technologies Group, CSIR Biosciences, Pretoria, South Africa.
Maxim ImakaevHarvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5320-2728
Dirk GrimmDepartment of Infectious Diseases/Virology, BioQuant Center, Heidelberg University Hospital, Heidelberg, Germany.
Kevin C WangDepartment of Dermatology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-5305-6791
Guoliang LiCollege of Informatics, Huazhong Agricultural University, Wuhan, China.ORCID http://orcid.org/0000-0003-1601-6640
Wing-Kin SungSchool of Computing, National University of Singapore, Singapore, Singapore.
Musa M MhlangaGene Expression and Biophysics Group, Division of Chemical, Systems and Synthetic Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. arhat@mhlangalab.org.ORCID http://orcid.org/0000-0003-1381-3409
University of Cape Town · ZAHeidelberg University · DEStanford University · USCouncil for Scientific and Industrial Research · ZAHarvard–MIT Division of Health Sciences and Technology · USHuazhong Agricultural University · CNNational University of Singapore · SGUniversity of Lisbon · PTUniversity of Udine · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Accumulation of trimethylation of histone H3 at lysine 4 (H3K4me3) on immune-related gene promoters underlies robust transcription during trained immunity. However, the molecular basis for this remains unknown. Here we show three-dimensional chromatin topology enables immune genes to engage in chromosomal contacts with a subset of long noncoding RNAs (lncRNAs) we have defined as immune gene-priming lncRNAs (IPLs). We show that the prototypical IPL, UMLILO, acts in cis to direct the WD repeat-containing protein 5 (WDR5)-mixed lineage leukemia protein 1 (MLL1) complex across the chemokine promoters, facilitating their H3K4me3 epigenetic priming. This mechanism is shared amongst several trained immune genes. Training mediated by β-glucan epigenetically reprograms immune genes by upregulating IPLs in manner dependent on nuclear factor of activated T cells. The murine chemokine topologically associating domain lacks an IPL, and the Cxcl genes are not trained. Strikingly, the insertion of UMLILO into the chemokine topologically associating domain in mouse macrophages resulted in training of Cxcl genes. This provides strong evidence that lncRNA-mediated regulation is central to the establishment of trained immunity.

Indexed as

AnimalsCell Line, TumorCell NucleusCells, CulturedChromatinEpigenesis, GeneticHeLa CellsHistone-Lysine N-MethyltransferaseHistonesHumansHuman Umbilical Vein Endothelial CellsMacrophagesMethylationMiceMyeloid-Lymphoid Leukemia ProteinPromoter Regions, GeneticChromatinhistone H3 trimethyl Lys4Histone-Lysine N-MethyltransferaseHistonesMyeloid-Lymphoid Leukemia ProteinRNA, Long Noncoding

Identifiers

PMID30531872
OpenAlexW2903023353

What OpenQuestion holds

Textmetadata
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.