Evidence map›Paper›PMID 35831302›Full record

ArticleNature communications2022

Bromodomain factor 5 is an essential regulator of transcription in Leishmania.

Nathaniel G Jones, Vincent Geoghegan, Gareth Moore, Juliana B T Carnielli, Katherine Newling, Félix Calderón, Raquel Gabarró, Julio Martín, Rab K Prinjha, Inmaculada Rioja and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.4field-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

11 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Identification of novel bromodomain inhibitors ofAntimicrobial agents and chemotherapy · 2024
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. 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

12 authors at 1 institution in 1 country.

Nathaniel G JonesYork Biomedical Research Institute, Department of Biology, University of York, York, UK. nathaniel.jones@york.ac.uk.ORCID 0000-0001-7328-4487
Vincent GeogheganYork Biomedical Research Institute, Department of Biology, University of York, York, UK.
Gareth MooreYork Biomedical Research Institute, Department of Biology, University of York, York, UK.
Juliana B T CarnielliYork Biomedical Research Institute, Department of Biology, University of York, York, UK.ORCID 0000-0003-2116-6379
Katherine NewlingYork Biomedical Research Institute, Department of Biology, University of York, York, UK.ORCID 0000-0003-0354-2924
Félix CalderónGSK Global Health, Tres Cantos, 28760, Madrid, Spain.ORCID 0000-0003-0486-6883
Raquel GabarróGSK Global Health, Tres Cantos, 28760, Madrid, Spain.
Julio MartínGSK Global Health, Tres Cantos, 28760, Madrid, Spain.
Rab K PrinjhaImmunology Research Unit, Research, R&D GSK, Gunnels Wood Road, Stevenage, Herts, SG1 2NY, UK.ORCID 0000-0002-2666-3326
Inmaculada RiojaImmunology Research Unit, Research, R&D GSK, Gunnels Wood Road, Stevenage, Herts, SG1 2NY, UK.
Anthony J WilkinsonYork Biomedical Research Institute and York Structural Biology Laboratory, Department of Chemistry, University of York, York, UK.ORCID 0000-0003-4577-9479
Jeremy C MottramYork Biomedical Research Institute, Department of Biology, University of York, York, UK.ORCID 0000-0001-5574-3766
University of York · GB

Funding

Medical Research Council MR/P027989/1Wellcome Trust 204829
6 · The paper itself

Abstract

Leishmania are unicellular parasites that cause human and animal diseases. Like other kinetoplastids, they possess large transcriptional start regions (TSRs) which are defined by histone variants and histone lysine acetylation. Cellular interpretation of these chromatin marks is not well understood. Eight bromodomain factors, the reader modules for acetyl-lysine, are found across Leishmania genomes. Using L. mexicana, Cas9-driven gene deletions indicate that BDF1-5 are essential for promastigotes. Dimerisable, split Cre recombinase (DiCre)-inducible gene deletion of BDF5 show it is essential for both promastigotes and murine infection. ChIP-seq identifies BDF5 as enriched at TSRs. XL-BioID proximity proteomics shows the BDF5 landscape is enriched for BDFs, HAT2, proteins involved in transcriptional activity, and RNA processing; revealing a Conserved Regulators of Kinetoplastid Transcription (CRKT) Complex. Inducible deletion of BDF5 causes global reduction in RNA polymerase II transcription. Our results indicate the requirement of Leishmania to interpret histone acetylation marks through the bromodomain-enriched CRKT complex for normal gene expression and cellular viability.

Indexed as

LeishmaniaAcetylationAnimalsFactor VHistonesHumansLysineMiceFactor VHistonesLysine

Identifiers

PMID35831302
PMCPMC9279504
OpenAlexW4285391636

What Socratic 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 Socratic graph.