Evidence map›Paper›PMID 31555818›Full record

ArticleNucleic acids research2019

Ash2l interacts with Oct4-stemness circuitry to promote super-enhancer-driven pluripotency network.

Ping-Hsing Tsai, Yueh Chien, Mong-Lien Wang, Chih-Hung Hsu, Benoit Laurent, Shih-Jie Chou, Wei-Chao Chang, Chian-Shiu Chien, Hsin-Yang Li, Hsin-Chen Lee and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

21 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Absent, Small, or Homeotic 2-Like-Mediated H3K4 Methylation and Nephrogenesis.Journal of the American Society of Nephrology : JASN · 2025
    Article
  4. Article
  5. Super-enhancer omics in stem cell.Molecular cancer · 2024
    Review
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  19. The complex activities of the SET1/MLL complex core subunits in development and disease.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020
    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

14 authors at 5 institutions in 3 countries.

Ping-Hsing TsaiDepartment of Medical Research, Taipei VeteransGeneral Hospital, Taipei 11217, Taiwan.
Yueh ChienDepartment of Medical Research, Taipei VeteransGeneral Hospital, Taipei 11217, Taiwan.
Mong-Lien WangDepartment of Medical Research, Taipei VeteransGeneral Hospital, Taipei 11217, Taiwan.
Chih-Hung HsuDepartment of Public Health, and Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China.
Benoit LaurentBoston Children's Hospital and Harvard Medical School, Boston MA 02115, USA.
Shih-Jie ChouDepartment of Medical Research, Taipei VeteransGeneral Hospital, Taipei 11217, Taiwan.
Wei-Chao ChangCenter for Molecular Medicine, China Medical University Hospital, Taichung 40447, Taiwan.
Chian-Shiu ChienDepartment of Medical Research, Taipei VeteransGeneral Hospital, Taipei 11217, Taiwan.
Hsin-Yang LiSchool of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
Hsin-Chen LeeInstitute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan.
Teh-Ia HuoInstitute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan.
Jui-Hung HungInstitutes of Data Science and Engineering, and Department of computer science, National Chiao-Tung University, Hsinchu 30010, Taiwan.
Chung-Hsuan ChenGenomic Research Center, Academia Sinica, Taipei 11529, Taiwan.
Shih-Hwa ChiouDepartment of Medical Research, Taipei VeteransGeneral Hospital, Taipei 11217, Taiwan.
National Yang Ming Chiao Tung University · TWBoston Children's Hospital · USChina Medical University · TWGenomics Research Center, Academia Sinica · TWWomen's Hospital, School of Medicine, Zhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pluripotency and cell fates can be modulated through the regulation of super-enhancers; however, the underlying mechanisms are unclear. Here, we showed a novel mechanism in which Ash2l directly binds to super-enhancers of several stemness genes to regulate pluripotency and self-renewal in pluripotent stem cells. Ash2l recruits Oct4/Sox2/Nanog (OSN) to form Ash2l/OSN complex at the super-enhancers of Jarid2, Nanog, Sox2 and Oct4, and further drives enhancer activation, upregulation of stemness genes, and maintains the pluripotent circuitry. Ash2l knockdown abrogates the OSN recruitment to all super-enhancers and further hinders the enhancer activation. In addition, CRISPRi/dCas9-mediated blocking of Ash2l-binding motifs at these super-enhancers also prevents OSN recruitment and enhancer activation, validating that Ash2l directly binds to super-enhancers and initiates the pluripotency network. Transfection of Ash2l with W118A mutation to disrupt Ash2l-Oct4 interaction fails to rescue Ash2l-driven enhancer activation and pluripotent gene upregulation in Ash2l-depleted pluripotent stem cells. Together, our data demonstrated Ash2l formed an enhancer-bound Ash2l/OSN complex that can drive enhancer activation, govern pluripotency network and stemness circuitry.

Indexed as

Enhancer Elements, GeneticAnimalsCell DifferentiationCell LineageCell Self RenewalCellular ReprogrammingCRISPR-Cas SystemsDNA-Binding ProteinsGene Expression Regulation, DevelopmentalHumansMiceMouse Embryonic Stem CellsMutationNanog Homeobox ProteinOctamer Transcription Factor-3Pluripotent Stem CellsAsh2l protein, mouseDNA-Binding ProteinsNanog Homeobox ProteinNanog protein, mouseOctamer Transcription Factor-3Pou5f1 protein, mouseSox2 protein, mouseSOXB1 Transcription FactorsTranscription Factors

Identifiers

PMID31555818
PMCPMC6821267
OpenAlexW2976063717

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.