Evidence map›Paper›PMID 31216473›Full record

ArticleCell reports2019

GR and LSD1/KDM1A-Targeted Gene Activation Requires Selective H3K4me2 Demethylation at Enhancers.

Erin A Clark, Feizhen Wu, Yirui Chen, Paco Kang, Ursula B Kaiser, Rui Fang, Yujiang G Shi

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

20 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Lysine-specific demethylase 1 as a corepressor of mineralocorticoid receptor.Hypertension research : official journal of the Japanese Society of Hypertension · 2022
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

7 authors at 3 institutions in 1 country.

Erin A ClarkDivision of Endocrinology, Diabetes and Hypertension, Departments of Medicine and BCMP, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Feizhen WuDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Yirui ChenDivision of Endocrinology, Diabetes and Hypertension, Departments of Medicine and BCMP, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Paco KangDivision of Endocrinology, Diabetes and Hypertension, Departments of Medicine and BCMP, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Ursula B KaiserDivision of Endocrinology, Diabetes and Hypertension, Departments of Medicine and BCMP, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Rui FangDivision of Endocrinology, Diabetes and Hypertension, Departments of Medicine and BCMP, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: rfang@bwh.harvard.edu.
Yujiang G ShiDivision of Endocrinology, Diabetes and Hypertension, Departments of Medicine and BCMP, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: yujiang_shi@hms.harvard.edu.
Harvard University · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · US

Funding

De-Regulation of 5hmC/TET2 Tumor Suppressor under Anti-Estrogen TherapyR01CA194302 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI SHI, YUJIANG GENO · 2016 to 2019
$1.6M
Post Translational Regulation of TET2 Function by Glucose SignalingR01GM112062 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI SHI, YUJIANG GENO · 2015 to 2018
$1.3M
NCI NIH HHS R01 CA194302NIGMS NIH HHS R01 GM112062
6 · The paper itself

Abstract

KDM1A-mediated H3K4 demethylation is a well-established mechanism underlying transcriptional gene repression, but its role in gene activation is less clear. Here, we report a critical function and mechanism of action of KDM1A in glucocorticoid receptor (GR)-mediated gene transcription. Biochemical purification of the nuclear GR complex revealed KDM1A as an integral component. In cell-free assays, GR modulates KDM1A-catalyzed H3K4 progressive demethylation by limiting the loss of H3K4me1. Similarly, in cells, KDM1A binds to most GR binding sites in the genome, where it removes preprogrammed H3K4me2 but leaves H3K4me1 untouched. Blocking KDM1A catalytic activity prevents H3K4me2 removal, severely impairs GR binding to chromatin, and dysregulates GR-targeted genes. Taken together, these data suggest KDM1A-mediated H3K4me2 demethylation at GRBSs promotes GR binding and plays an important role in glucocorticoid-induced gene transcription, broadening the mechanisms that contribute to nuclear receptor-mediated gene activation.

Indexed as

Enhancer Elements, GeneticGene Expression RegulationTranscriptional ActivationA549 CellsChromatinDemethylationHeLa CellsHistone DemethylasesHistonesHumansPromoter Regions, GeneticReceptors, GlucocorticoidChromatinHistone DemethylasesHistonesKDM1A protein, humanReceptors, GlucocorticoiddexamethasoneenhancerglucocorticoidH3K27acH3K4me2histone demethylaseKDM1ALSD1nuclear receptorpreprogramming

Identifiers

PMID31216473
PMCPMC7433711
OpenAlexW2949088158

What OpenQuestion 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 OpenQuestion graph.