Evidence map›Paper›PMID 26751588›Full record

ArticlePloS one2016

The Histone Demethylase PHF8 Is Essential for Endothelial Cell Migration.

Lunda Gu, Juliane Hitzel, Franziska Moll, Christoph Kruse, Randa Abdel Malik, Jens Preussner, Mario Looso, Matthias S Leisegang, Dieter Steinhilber, Ralf P Brandes and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Genes & development · 2024
    Article
  4. Article
  5. KDM7 Demethylases: Regulation, Function and Therapeutic Targeting.Advances in experimental medicine and biology · 2023
    Article
  6. Review
  7. Variants inHGG advances · 2022
    Article
  8. Epigenetics in blood-brain barrier disruption.Fluids and barriers of the CNS · 2021
    Review
  9. Article
  10. Histone methylation and vascular biology.Clinical epigenetics · 2020
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. 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

11 authors at 2 institutions in 1 country.

Lunda GuInstitute for Cardiovascular Physiology, Medical Faculty, Goethe-University Frankfurt, Germany.
Juliane HitzelInstitute for Cardiovascular Physiology, Medical Faculty, Goethe-University Frankfurt, Germany.
Franziska MollInstitute for Cardiovascular Physiology, Medical Faculty, Goethe-University Frankfurt, Germany.
Christoph KruseInstitute for Cardiovascular Physiology, Medical Faculty, Goethe-University Frankfurt, Germany.
Randa Abdel MalikInstitute of Vascular Signalling, Centre for Molecular Medicine, Goethe-University Frankfurt, Germany.
Jens PreussnerMax Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Mario LoosoMax Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Matthias S LeisegangInstitute for Cardiovascular Physiology, Medical Faculty, Goethe-University Frankfurt, Germany.
Dieter SteinhilberInstitute of Pharmaceutical Chemistry/ZAFES, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Ralf P BrandesInstitute for Cardiovascular Physiology, Medical Faculty, Goethe-University Frankfurt, Germany.
Christian ForkInstitute for Cardiovascular Physiology, Medical Faculty, Goethe-University Frankfurt, Germany.
German Centre for Cardiovascular Research · DEGoethe University Frankfurt · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epigenetic marks critically control gene expression and thus the cellular activity state. The functions of many epigenetic modifiers in the vascular system have not yet been studied. We screened for histone modifiers in endothelial cells and observed a fairly high expression of the histone plant homeodomain finger protein 8 (PHF8). Given its high expression, we hypothesize that this histone demethylase is important for endothelial cell function. Overexpression of PHF8 catalyzed the removal of methyl-groups from histone 3 lysine 9 (H3K9) and H4K20, whereas knockdown of the enzyme increased H3K9 methylation. Knockdown of PHF8 by RNAi also attenuated endothelial proliferation and survival. As a functional readout endothelial migration and tube formation was studied. PHF8 siRNA attenuated the capacity for migration and developing of capillary-like structures. Given the impact of PHF8 on cell cycle genes, endothelial E2F transcription factors were screened, which led to the identification of the gene repressor E2F4 to be controlled by PHF8. Importantly, PHF8 maintains E2F4 but not E2F1 expression in endothelial cells. Consistently, chromatin immunoprecipitation revealed that PHF8 reduces the H3K9me2 level at the E2F4 transcriptional start site, demonstrating a direct function of PHF8 in endothelial E2F4 gene regulation. Conclusion: PHF8 by controlling E2F4 expression maintains endothelial function.

Indexed as

Cell MovementApoptosisCatalysisCell LineCell ProliferationCell SurvivalDNA MethylationE2F4 Transcription FactorEndothelial CellsGene Expression RegulationGene Knockdown TechniquesHEK293 CellsHistone DemethylasesHistonesHumansHuman Umbilical Vein Endothelial CellsE2F4 protein, humanE2F4 Transcription FactorHistone DemethylasesHistonesPHF8 protein, humanRNA, MessengerRNA, Small InterferingTranscription Factors

Identifiers

PMID26751588
PMCPMC4713448
OpenAlexW2237201885

What OpenQuestion 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 OpenQuestion graph.