Evidence map›Paper›PMID 21423269›Full record

ArticleCell research2011

Smek promotes histone deacetylation to suppress transcription of Wnt target gene brachyury in pluripotent embryonic stem cells.

Jungmook Lyu, Eek-Hoon Jho, Wange Lu

Open access · bronzeAbstract read
In one paragraph

Article in Cell research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

25 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. H3K27ac Is Essential for Human Naive Pluripotency Modulated by m6A-Driven EP300 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. SMEK1 promotes lung adenocarcinoma proliferation and invasion by activating Wnt/β-catenin signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Smek1/2 is a nuclear chaperone and cofactor for cleaved Wnt receptor Ryk, regulating cortical neurogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  15. Article
  16. Article
  17. Distinct phosphatases antagonize the p53 response in different phases of the cell cycle.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  18. Article
  19. Article
  20. 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

3 authors at 3 institutions in 2 countries.

Jungmook LyuThe Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA. kohono@kuhp.kyoto-u.ac.jp
Eek-Hoon Jho
Wange Lu
Broad Center · USUniversity of Seoul · KRUniversity of Southern California · US

Funding

Molecular Mechanisms of Neuronal DifferentiationR01NS067213 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LU, WANGE · 2010 to 2014
$1.7M
NINDS NIH HHS 1R01NS067213-01A1NINDS NIH HHS R01 NS067213
6 · The paper itself

Abstract

In embryonic stem cells (ESCs), Wnt-responsive development-related genes are silenced to maintain pluripotency and their expression is activated during differentiation. Acetylation of histones by histone acetyltransferases stimulates transcription, whereas deacetylation of histones by HDACs is correlated with transcriptional repression. Although Wnt-mediated gene transcription has been intimately linked to the acetylation or deacetylation of histones, how Wnt signaling regulates this type of histone modification is poorly understood. Here, we report that Smek, a regulatory subunit of protein phosphatase 4 (PP4) complex, plays an important role in histone deacetylation and silencing of the Wnt-responsive gene, brachyury, in ESCs. Smek mediates recruitment of PP4c and HDAC1 to the Tcf/Lef binding site of the brachyury promoter and inhibits brachyury expression in ESCs. Activation of Wnt signaling during differentiation causes disruption of the Smek/PP4c/HDAC1 complex, resulting in an increase in histones H3 and H4 acetylation at the brachyury gene locus. These results suggest that the Smek-containing PP4 complex represses transcription of Wnt-responsive development-related genes through histone deacetylation, and that this complex is essential for ESC pluripotency maintenance.

Indexed as

AcetylationAlkaline PhosphataseAnimalsbeta CateninBrachyury ProteinCell DifferentiationCell NucleusCells, CulturedDown-RegulationFetal ProteinsGene Expression RegulationGoosecoid ProteinHistone Deacetylase 1HistonesHomeodomain ProteinsHumansAlkaline Phosphatasebeta CateninBrachyury ProteinFetal ProteinsGoosecoid ProteinGsc protein, mouseHdac1 protein, mouseHistone Deacetylase 1HistonesHomeodomain Proteinsinsulin gene enhancer binding protein Isl-1LIM-Homeodomain ProteinsMultiprotein ComplexesPhosphoprotein PhosphatasesPpp4r3a protein, mouseSmek2 protein, mouseT-Box Domain ProteinsTranscription FactorsVascular Endothelial Growth Factor Receptor-2Wnt Proteins

Identifiers

PMID21423269
PMCPMC3203701
OpenAlexW1998131796

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.