Evidence map›Paper›PMID 27595565›Full record

ArticleeLife2016

Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1.

Joseph S Harrison, Evan M Cornett, Dennis Goldfarb, Paul A DaRosa, Zimeng M Li, Feng Yan, Bradley M Dickson, Angela H Guo, Daniel V Cantu, Lilia Kaustov and 9 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
7.5field-weighted citation impact, top 2% 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

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.

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21 more citing papers are in PubMed but not listed here.

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

19 authors at 4 institutions in 2 countries.

Joseph S HarrisonDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Evan M CornettCenter for Epigenetics, Van Andel Research Institute, Grand Rapids, United States.
Dennis GoldfarbDepartment of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Paul A DaRosaDepartment of Biochemistry, University of Washington, Seattle, United States.
Zimeng M LiDepartment of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Feng YanDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Bradley M DicksonCenter for Epigenetics, Van Andel Research Institute, Grand Rapids, United States.
Angela H GuoDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Daniel V CantuDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Lilia KaustovStructural Genomics Consortium, University of Toronto, Toronto, Canada.
Peter J BrownStructural Genomics Consortium, University of Toronto, Toronto, Canada.
Cheryl H ArrowsmithStructural Genomics Consortium, University of Toronto, Toronto, Canada.
Dorothy A ErieDepartment of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Michael B MajorDepartment of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Rachel E KlevitDepartment of Biochemistry, University of Washington, Seattle, United States.
Krzysztof KrajewskiDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, United States.ORCID 0000-0001-7159-617X
Brian KuhlmanDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Brian D StrahlDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Scott B RothbartCenter for Epigenetics, Van Andel Research Institute, Grand Rapids, United States.ORCID 0000-0003-1631-5392
University of North Carolina at Chapel Hill · USUniversity of Toronto · CAVan Andel Institute · USUniversity of Washington · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
Integrated Training in Cancer Model SystemsT32CA009156 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 1985 to 2020
$19.7M
Structural and Functional Characterization of BRCA1/BARD1R01GM088055 · NIGMS · UNIVERSITY OF WASHINGTON · PI KLEVIT, RACHEL E · 2009 to 2020
$6.5M
Designing Affinity and Specificity at Protein InterfacesR01GM073960 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KUHLMAN, BRIAN A · 2005 to 2018
$3.1M
Structure Function Studies of DNA Mismatch RepairR01GM079480 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ERIE, DOROTHY A · 2007 to 2017
$2.7M
Factors that regulate chromatin organization and gene transcriptionR01GM110058 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STRAHL, BRIAN D · 2014 to 2017
$1.2M
Mechanisms Regulating DNA Methylation Maintenance in ChromatinR00CA181343 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI ROTHBART, SCOTT · 2015 to 2017
$746k
Mechanisms Regulating DNA Methylation Maintenance in ChromatinK99CA181343 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROTHBART, SCOTT · 2014 to 2015
$211k
NCI NIH HHS K99 CA181343NCI NIH HHS P30 CA016086NCI NIH HHS R00 CA181343NCI NIH HHS T32 CA009156NIGMS NIH HHS R01 GM073960NIGMS NIH HHS R01 GM079480NIGMS NIH HHS R01 GM088055NIGMS NIH HHS R01 GM110058NIGMS NIH HHS T32 GM007270Wellcome Trust
6 · The paper itself

Abstract

The epigenetic inheritance of DNA methylation requires UHRF1, a histone- and DNA-binding RING E3 ubiquitin ligase that recruits DNMT1 to sites of newly replicated DNA through ubiquitylation of histone H3. UHRF1 binds DNA with selectivity towards hemi-methylated CpGs (HeDNA); however, the contribution of HeDNA sensing to UHRF1 function remains elusive. Here, we reveal that the interaction of UHRF1 with HeDNA is required for DNA methylation but is dispensable for chromatin interaction, which is governed by reciprocal positive cooperativity between the UHRF1 histone- and DNA-binding domains. HeDNA recognition activates UHRF1 ubiquitylation towards multiple lysines on the H3 tail adjacent to the UHRF1 histone-binding site. Collectively, our studies are the first demonstrations of a DNA-protein interaction and an epigenetic modification directly regulating E3 ubiquitin ligase activity. They also define an orchestrated epigenetic control mechanism involving modifications both to histones and DNA that facilitate UHRF1 chromatin targeting, H3 ubiquitylation, and DNA methylation inheritance.

Indexed as

DNA MethylationEpigenesis, GeneticUbiquitinationWillsCCAAT-Enhancer-Binding ProteinsDNADNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesHeLa CellsHistonesHumansProtein BindingUbiquitin-Protein LigasesCCAAT-Enhancer-Binding ProteinsDNADNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNMT1 protein, humanHistonesUbiquitin-Protein LigasesUHRF1 protein, humanbiochemistrybiophysicsDNA methylationepigeneticshistone post-translational modificationshumanstructural biologyubiquitinubiquitylationUHRF1

Identifiers

PMID27595565
PMCPMC5012860
OpenAlexW2508535406

What OpenQuestion holds

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Registered trials

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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.