Evidence map›Paper›PMID 27281824›Full record

ArticleThe Journal of biological chemistry2016

Mechanism of Histone H3K4me3 Recognition by the Plant Homeodomain of Inhibitor of Growth 3.

Sophia Kim, Senthil Natesan, Gabriel Cornilescu, Samuel Carlson, Marco Tonelli, Urszula L McClurg, Olivier Binda, Craig N Robson, John L Markley, Stefan Balaz and 1 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

22 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. The TUDOR domain of SMN is an H3K79Life science alliance · 2023
    Article
  7. Article
  8. Article
  9. Article
  10. AnPeerJ · 2022
    Article
  11. Article
  12. Review
  13. Understanding the interplay between CpG island-associated gene promoters and H3K4 methylation.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  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

11 authors at 3 institutions in 2 countries.

Sophia KimFrom the Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, Vermont 05446.
Senthil NatesanFrom the Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, Vermont 05446.
Gabriel Cornilescuthe National Magnetic Resonance Facility at Madison and Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, and.
Samuel CarlsonFrom the Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, Vermont 05446.
Marco Tonellithe National Magnetic Resonance Facility at Madison and Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, and.
Urszula L McClurgthe Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne NE2 4HH, United Kingdom.
Olivier Bindathe Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne NE2 4HH, United Kingdom.
Craig N Robsonthe Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne NE2 4HH, United Kingdom.
John L Markleythe National Magnetic Resonance Facility at Madison and Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, and.
Stefan BalazFrom the Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, Vermont 05446.
Karen C GlassFrom the Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, Vermont 05446, karen.glass@acphs.edu.ORCID 0000-0002-2761-733X
Albany College of Pharmacy and Health Sciences · USNewcastle University · GBUniversity of Wisconsin–Madison · US

Funding

WATER DISTRIB:PHYSICAL PROPERT:PIZZA &LMPS MOZZARELLA CHEESES:EARLY STAGE MATURP41RR002301 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 1985 to 2011
$13.0M
TR&D 3: TECHNOLOGY DEVELOPMENT FOR NMR STUDIES OF SMALL MOLECULES (METABOLOMICS, NATURAL PRODUCTS, METABOLITE-PROTEIN INTERACTIONS) pp.537-585 P41GM103399 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 2012 to 2019
$9.4M
Integrated state-of-the-art LC-MS/NMR system for the University of WisconsinS10RR025062 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 2008 to 2008
$1.7M
Conceptual Prediction of Drug Bioactivities in Cell-Based Assays: cell-QSARR01GM080508 · NIGMS · ALBANY COLLEGE OF PHARMACY · PI BALAZ, STEFAN · 2009 to 2013
$1.3M
Upgrade of the NMRFAM 750 MHz NMR SpectrometerS10RR029220 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 2010 to 2010
$766k
NMR Spectrometer System Optimized for Direct 13C or 15N DetectionS10RR023438 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 2008 to 2008
$500k
CONSOLE UPGRADES FOR NMR FACILITYS10RR008438 · NCRR · UNIVERSITY OF WISCONSIN MADISON · PI MARKLEY, JOHN L · 1993 to 1993
–
WIDE-BORE 9.4 TESLA NMR SPECTROMETER FOR UW-MADISONS10RR002781 · NCRR · UNIVERSITY OF WISCONSIN MADISON · PI MARKLEY, JOHN L · 1986 to 1986
–
Breast Cancer Now 2013MAYSP005NCRR NIH HHS P41 RR002301NCRR NIH HHS S10 RR002781NCRR NIH HHS S10 RR008438NCRR NIH HHS S10 RR023438NCRR NIH HHS S10 RR025062NCRR NIH HHS S10 RR029220NIGMS NIH HHS P41 GM103399NIGMS NIH HHS R01 GM080508Prostate Cancer UK PG09-23
6 · The paper itself

Abstract

Aberrant access to genetic information disrupts cellular homeostasis and can lead to cancer development. One molecular mechanism that regulates access to genetic information includes recognition of histone modifications, which is carried out by protein modules that interact with chromatin and serve as landing pads for enzymatic activities that regulate gene expression. The ING3 tumor suppressor protein contains a plant homeodomain (PHD) that reads the epigenetic code via recognition of histone H3 tri-methylated at lysine 4 (H3K4me3), and this domain is lost or mutated in various human cancers. However, the molecular mechanisms targeting ING3 to histones and the role of this interaction in the cell remain elusive. Thus, we employed biochemical and structural biology approaches to investigate the interaction of the ING3 PHD finger (ING3PHD) with the active transcription mark H3K4me3. Our results demonstrate that association of the ING3PHD with H3K4me3 is in the sub-micromolar range (KD ranging between 0.63 and 0.93 μm) and is about 200-fold stronger than with the unmodified histone H3. NMR and computational studies revealed an aromatic cage composed of Tyr-362, Ser-369, and Trp-385 that accommodate the tri-methylated side chain of H3K4. Mutational analysis confirmed the critical importance of Tyr-362 and Trp-385 in mediating the ING3PHD-H3K4me3 interaction. Finally, the biological relevance of ING3PHD-H3K4me3 binding was demonstrated by the failure of ING3PHD mutant proteins to enhance ING3-mediated DNA damage-dependent cell death. Together, our results reveal the molecular mechanism of H3K4me3 selection by the ING3PHD and suggest that this interaction is important for mediating ING3 tumor suppressive activities.

Indexed as

Amino Acid SubstitutionCell DeathDNA DamageEpigenesis, GeneticHistonesHomeodomain ProteinsHumansMethylationMutation, MissenseNuclear Magnetic Resonance, BiomolecularRING Finger DomainsTumor Suppressor ProteinsHistonesHomeodomain ProteinsING3 protein, humanTumor Suppressor Proteinsepigeneticshistone acetyltransferasehistone methylationInhibitor of Growth 3isothermal titration calorimetry (ITC)nuclear magnetic resonance (NMR)PHD fingerplant homeodomain

Identifiers

PMID27281824
PMCPMC5000080
OpenAlexW2411087639

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.