Evidence map›Paper›PMID 26073541›Full record

ArticleMolecular cell2015

Engineering of a Histone-Recognition Domain in Dnmt3a Alters the Epigenetic Landscape and Phenotypic Features of Mouse ESCs.

Kyung-Min Noh, Haibo Wang, Hyunjae R Kim, Wendy Wenderski, Fang Fang, Charles H Li, Scott Dewell, Stephen H Hughes, Ari M Melnick, Dinshaw J Patel and 2 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.

  1. Pooled it
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  16. Enzymology of Mammalian DNA Methyltransferases.Advances in experimental medicine and biology · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Kyung-Min Noh *Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA.
Haibo Wang *Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, P.R. China.
Hyunjae R KimLaboratory of RNA Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
Wendy WenderskiLaboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA.
Fang FangDepartment of Medicine, Hematology-Oncology, Weill Cornell Medical College, New York, NY 10021, USA.
Charles H LiLaboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA.
Scott DewellGenomics, Resource Center, The Rockefeller University, New York, NY 10065, USA.
Stephen H HughesIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Ari M MelnickDepartment of Medicine, Hematology-Oncology, Weill Cornell Medical College, New York, NY 10021, USA.
Dinshaw J PatelStructure Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Haitao LiDepartment of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, P.R. China.
C David AllisLaboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA.
Rockefeller University · USCornell University · USTsinghua University · CNEuropean Molecular Biology Laboratory · DEMemorial Sloan Kettering Cancer Center · USNational Cancer Institute · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Elisa de Stanchina · 1985 to 2026
$347.4M
REPRESSIVE HISTONE AND DNA METHYLATION IN RODENT DEPRESSION MODELSP50MH096890 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI TAMMINGA, CAROL A · 2012 to 2021
$20.2M
IntegraseZIABC011426 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HUGHES, STEPHEN H · 2012 to 2022
$14.0M
INFLUENCE OF HISTONE H1 AND HMGS ON GENE EXPRESSIONR01GM040922 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI ALLIS, CHARLES DAVID · 1989 to 2022
$10.0M
Epigenomic Profile and Function of H3.3 Variant During Sensitive Period of NeurodR01MH094698 · NIMH · ROCKEFELLER UNIVERSITY · PI ALLIS, CHARLES DAVID · 2011 to 2015
$2.1M
NCI NIH HHS P30 CA008748NIMH NIH HHS MH 094698NIMH NIH HHS P50 MH096890NIMH NIH HHS R01 MH094698
6 · The paper itself

Abstract

Histone modification and DNA methylation are associated with varying epigenetic "landscapes," but detailed mechanistic and functional links between the two remain unclear. Using the ATRX-DNMT3-DNMT3L (ADD) domain of the DNA methyltransferase Dnmt3a as a paradigm, we apply protein engineering to dissect the molecular interactions underlying the recruitment of this enzyme to specific regions of chromatin in mouse embryonic stem cells (ESCs). By rendering the ADD domain insensitive to histone modification, specifically H3K4 methylation or H3T3 phosphorylation, we demonstrate the consequence of dysregulated Dnmt3a binding and activity. Targeting of a Dnmt3a mutant to H3K4me3 promoters decreases gene expression in a subset of developmental genes and alters ESC differentiation, whereas aberrant binding of another mutant to H3T3ph during mitosis promotes chromosome instability. Our studies support the general view that histone modification "reading" and DNA methylation are closely coupled in mammalian cells, and suggest an avenue for the functional assessment of chromatin-associated proteins.

Indexed as

Protein EngineeringAnimalsCell DifferentiationDNA (Cytosine-5-)-MethyltransferasesDNA HelicasesDNA MethylationDNA Methyltransferase 3AEmbryonic Stem CellsHistonesMiceMice, Inbred C57BLMitosisNuclear ProteinsPhosphorylationPromoter Regions, GeneticProtein Structure, TertiaryAtrx protein, mouseDNA (Cytosine-5-)-MethyltransferasesDNA HelicasesDNA Methyltransferase 3ADnmt3a protein, mouseDnmt3l protein, mouseHistonesNuclear ProteinsX-linked Nuclear Protein

Identifiers

PMID26073541
PMCPMC4491196
OpenAlexW1551800042

What OpenQuestion holds

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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.