Evidence map›Paper›PMID 32023463›Full record

ArticleCell reports2020

Oct4-Mediated Inhibition of Lsd1 Activity Promotes the Active and Primed State of Pluripotency Enhancers.

Lama AlAbdi, Debapriya Saha, Ming He, Mohd Saleem Dar, Sagar M Utturkar, Putu Ayu Sudyanti, Stephen McCune, Brice H Spears, James A Breedlove, Nadia A Lanman and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-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

15 citing papers in PubMed, 39 citations in OpenAlex.

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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.

Lama AlAbdiDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Debapriya SahaDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Ming HeDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Mohd Saleem DarDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Sagar M UtturkarPurdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
Putu Ayu SudyantiDepartment of Statistics, Purdue University, West Lafayette, IN 47907, USA.
Stephen McCuneDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Brice H SpearsDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
James A BreedloveDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Nadia A LanmanPurdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA; Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.
Humaira GowherDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA; Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address: hgowher@purdue.edu.
Purdue University West Lafayette · USCenter for Cancer Research · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Transgenic Mouse Core Facility Shared Resource (TMCF-SR)P30CA023168 · NCI · PURDUE UNIVERSITY WEST LAFAYETTE · PI Andrea L Kasinski · 1985 to 2026
$43.4M
Regulation of Dnmt3 Activity at Enhancers of Cell Identity Genes During DifferentiationR01GM118654 · NIGMS · PURDUE UNIVERSITY · PI GOWHER, HUMAIRA · 2017 to 2021
$1.6M
NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA023168NIGMS NIH HHS R01 GM118654
6 · The paper itself

Abstract

An aberrant increase in pluripotency gene (PpG) expression due to enhancer reactivation could induce stemness and enhance the tumorigenicity of cancer stem cells. Silencing of PpG enhancers (PpGe) during embryonic stem cell differentiation involves Lsd1-mediated H3K4me1 demethylation and DNA methylation. Here, we observed retention of H3K4me1 and DNA hypomethylation at PpGe associated with a partial repression of PpGs in F9 embryonal carcinoma cells (ECCs) post-differentiation. H3K4me1 demethylation in F9 ECCs could not be rescued by Lsd1 overexpression. Given our observation that H3K4me1 demethylation is accompanied by strong Oct4 repression in P19 ECCs, we tested if Oct4 interaction with Lsd1 affects its catalytic activity. Our data show a dose-dependent inhibition of Lsd1 activity by Oct4 and retention of H3K4me1 at PpGe in Oct4-overexpressing P19 ECCs. These data suggest that Lsd1-Oct4 interaction in cancer stem cells could establish a "primed" enhancer state that is susceptible to reactivation, leading to aberrant PpG expression.

Indexed as

Enhancer Elements, GeneticBiocatalysisCarcinoma, EmbryonalCell DifferentiationCell Line, TumorChromatinDNA MethylationEpigenesis, GeneticHistone DemethylasesHistonesHumansMaleModels, BiologicalOctamer Transcription Factor-3Pluripotent Stem CellsChromatinHistone DemethylasesHistonesKDM1A protein, humanOctamer Transcription Factor-3POU5F1 protein, humancancer stem cellsDNA methylationDnmt3aembryonal carcinoma cellsenhancer primingenhancershistone demethylationLsd1Oct4pluripotency

Identifiers

PMID32023463
PMCPMC7316367
OpenAlexW3004668405

What OpenQuestion holds

Textmetadata
LicenceTDM
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.