Evidence map›Paper›PMID 27168161›Full record

ArticleStem cells and development2016

Identification of Novel EZH2 Targets Regulating Osteogenic Differentiation in Mesenchymal Stem Cells.

Sarah Hemming, Dimitrios Cakouros, Kate Vandyke, Melissa J Davis, Andrew C W Zannettino, Stan Gronthos

Open access · greenAbstract read
In one paragraph

Article in Stem cells and development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

40 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Molecular and Cellular Mechanisms of Osteoporosis.International journal of molecular sciences · 2023
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Genetics and Epigenetics of Bone Remodeling and Metabolic Bone Diseases.International journal of molecular sciences · 2022
    Review
  14. Article
  15. Review
  16. Epigenetic therapy attenuates oxidative stress in BMSCs during ageing.Journal of cellular and molecular medicine · 2022
    Article
  17. Article
  18. Review
  19. Review
  20. Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics.International journal of molecular sciences · 2021
    Review
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

6 authors at 2 institutions in 1 country.

Sarah Hemming1 Mesenchymal Stem Cell Laboratory, Faculty of Health Sciences, School of Medicine, The University of Adelaide , Adelaide, Australia .
Dimitrios Cakouros1 Mesenchymal Stem Cell Laboratory, Faculty of Health Sciences, School of Medicine, The University of Adelaide , Adelaide, Australia .
Kate Vandyke2 Cancer Theme, South Australian Health and Medical Research Institute , Adelaide, Australia .
Melissa J Davis5 Division of Bioinformatics, Walter and Eliza Hall Institute for Medical Research , Melbourne, Australia .
Andrew C W Zannettino2 Cancer Theme, South Australian Health and Medical Research Institute , Adelaide, Australia .
Stan Gronthos1 Mesenchymal Stem Cell Laboratory, Faculty of Health Sciences, School of Medicine, The University of Adelaide , Adelaide, Australia .
South Australian Health and Medical Research Institute · AUSouth Australia Pathology · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Histone three lysine 27 (H3K27) methyltransferase enhancer of zeste homolog 2 (EZH2) is a critical epigenetic modifier, which regulates gene transcription through the trimethylation of the H3K27 residue leading to chromatin compaction and gene repression. EZH2 has previously been identified to regulate human bone marrow-derived mesenchymal stem cells (MSC) lineage specification. MSC lineage specification is regulated by the presence of EZH2 and its H3K27me3 modification or the removal of the H3K27 modification by lysine demethylases 6A and 6B (KDM6A and KDM6B). This study used a bioinformatics approach to identify novel genes regulated by EZH2 during MSC osteogenic differentiation. In this study, we identified the EZH2 targets, ZBTB16, MX1, and FHL1, which were expressed at low levels in MSC. EZH2 and H3K27me3 were found to be present along the transcription start site of their respective promoters. During osteogenesis, these genes become actively expressed coinciding with the disappearance of EZH2 and H3K27me3 on the transcription start site of these genes and the enrichment of the active H3K4me3 modification. Overexpression of EZH2 downregulated the transcript levels of ZBTB16, MX1, and FHL1 during osteogenesis. Small interfering RNA targeting of MX1 and FHL1 was associated with a downregulation of the key osteogenic transcription factor, RUNX2, and its downstream targets osteopontin and osteocalcin. These findings highlight that EZH2 not only acts through the direct regulation of signaling modules and lineage-specific transcription factors but also targets many novel genes important for mediating MSC osteogenic differentiation.

Indexed as

Cell DifferentiationOsteogenesisAdultChromatin ImmunoprecipitationEnhancer of Zeste Homolog 2 ProteinGene Knockdown TechniquesHistonesHumansIntracellular Signaling Peptides and ProteinsLIM Domain ProteinsLysineMesenchymal Stem CellsMethylationMuscle ProteinsMyxovirus Resistance ProteinsOsteoblastsEnhancer of Zeste Homolog 2 ProteinFHL1 protein, humanHistonesIntracellular Signaling Peptides and ProteinsLIM Domain ProteinsLysineMuscle ProteinsMX1 protein, humanMyxovirus Resistance ProteinsRepressor ProteinsRNA, Small Interfering

Identifiers

PMID27168161
PMCPMC4928132
OpenAlexW2348269067

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.