Evidence map›Paper›PMID 26523391›Full record

ArticleeLife2015

ETO family protein Mtgr1 mediates Prdm14 functions in stem cell maintenance and primordial germ cell formation.

Nataliya Nady, Ankit Gupta, Ziyang Ma, Tomek Swigut, Akiko Koide, Shohei Koide, Joanna Wysocka

Open access · goldAbstract read
In one paragraph

Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

38 citing papers in PubMed, 55 citations in OpenAlex.

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  11. Early Gonadal Development and Sex Determination in Mammal.International journal of molecular sciences · 2022
    Review
  12. Article
  13. Review
  14. Histone 3 Lysine 27 Trimethylation Signature in Breast Cancer.International journal of molecular sciences · 2021
    Review
  15. Review
  16. Article
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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

7 authors at 3 institutions in 1 country.

Nataliya NadyDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States.
Ankit GuptaDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States.
Ziyang MaDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States.
Tomek SwigutDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States.
Akiko KoideDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States.
Shohei KoideDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States.
Joanna WysockaDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States.
Stanford University · USUniversity of Chicago · USNational Institute of Environmental Health Sciences · US

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI MARK W. LINGEN · 1985 to 2026
$122.1M
Rational generation of directed protein-capture reagentsR01GM090324 · NIGMS · UNIVERSITY OF CHICAGO · PI KOIDE, SHOHEI · 2009 to 2013
$2.6M
Genetically encoded designer inhibitors for functional epigenomicsR01DA036887 · NIDA · UNIVERSITY OF CHICAGO · PI KOIDE, SHOHEI · 2013 to 2017
$2.0M
Chromatin remodeling in multipotent neural crest formation and CHARGE syndromeR01GM095555 · NIGMS · STANFORD UNIVERSITY · PI WYSOCKA, JOANNA · 2010 to 2014
$1.5M
Mechanisms of enhancer activation in early developmentR01GM112720 · NIGMS · STANFORD UNIVERSITY · PI WYSOCKA, JOANNA · 2015 to 2018
$1.2M
A Novel Prdm14-containing Protein Complex Regulates Chromatin in Stem Cells, Development, and CancerK99CA212204 · NCI · STANFORD UNIVERSITY · PI NADY, NATALIYA HERZANYCH · 2016 to 2017
$203k
Canadian Institutes of Health ResearchHoward Hughes Medical InstituteNCI NIH HHS K99 CA212204NCI NIH HHS P30 CA014599NIDA NIH HHS R01 DA036887NIDA NIH HHS R01DA036887NIGMS NIH HHS R01 GM090324NIGMS NIH HHS R01GM090324NIGMS NIH HHS R01 GM095555NIGMS NIH HHS R01 GM112720NIGMS NIH HHS R01GM112720
6 · The paper itself

Abstract

Prdm14 is a sequence-specific transcriptional regulator of embryonic stem cell (ESC) pluripotency and primordial germ cell (PGC) formation. It exerts its function, at least in part, through repressing genes associated with epigenetic modification and cell differentiation. Here, we show that this repressive function is mediated through an ETO-family co-repressor Mtgr1, which tightly binds to the pre-SET/SET domains of Prdm14 and co-occupies its genomic targets in mouse ESCs. We generated two monobodies, synthetic binding proteins, targeting the Prdm14 SET domain and demonstrate their utility, respectively, in facilitating crystallization and structure determination of the Prdm14-Mtgr1 complex, or as genetically encoded inhibitor of the Prdm14-Mtgr1 interaction. Structure-guided point mutants and the monobody abrogated the Prdm14-Mtgr1 association and disrupted Prdm14's function in mESC gene expression and PGC formation in vitro. Altogether, our work uncovers the molecular mechanism underlying Prdm14-mediated repression and provides renewable reagents for studying and controlling Prdm14 functions.

Indexed as

GametogenesisGene Expression RegulationAnimalsCrystallography, X-RayDNA-Binding ProteinsDNA Mutational AnalysisEmbryonic Stem CellsGerm CellsMiceProtein BindingProtein ConformationRepressor ProteinsRNA-Binding ProteinsTranscription FactorsCBFA2T2 myeloid-transforming gene-related proteinDNA-Binding ProteinsPrdm14 protein, mouseRepressor ProteinsRNA-Binding ProteinsTranscription Factorsbiophysicsdevelopmental biologyembryonic stem cellsepigeneticsgenomicsmonobodymouseprimordial Germ Cellsstem cellsstructural biologyX-ray crystallography

Identifiers

PMID26523391
PMCPMC4749557
OpenAlexW2229306392

What OpenQuestion holds

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LicenceCC BY
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.