Evidence map›Paper›PMID 25104842›Full record

ArticleMolecular & cellular proteomics : MCP2014

A PWWP domain-containing protein targets the NuA3 acetyltransferase complex via histone H3 lysine 36 trimethylation to coordinate transcriptional elongation at coding regions.

Tonya M Gilbert, Stephen L McDaniel, Stephanie D Byrum, Jessica A Cades, Blair C R Dancy, Herschel Wade, Alan J Tackett, Brian D Strahl, Sean D Taverna

Abstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
–field-weighted citation impact
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

42 citing papers in PubMed.

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  9. Frontiers in epigenetics and epigenomics · 2024
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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

9 authors.

Tonya M GilbertFrom the ‡Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; §Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205;
Stephen L McDaniel¶Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599;
Stephanie D Byrum‖Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205;
Jessica A CadesFrom the ‡Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205;
Blair C R DancyFrom the ‡Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; §Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205;
Herschel Wade**Department of Biophysics and Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205;
Alan J Tackett‖Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205;
Brian D Strahl¶Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599; ‡‡Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599 staverna@jhmi.edu brian_strahl@med.unc.edu.
Sean D TavernaFrom the ‡Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; §Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205; staverna@jhmi.edu brian_strahl@med.unc.edu.

Funding

Understanding Hesitant AdoptersP20GM103429 · NIGMS · UNIV OF ARKANSAS FOR MED SCIS · PI Lawrence E Cornett, JERRY WARE · 2012 to 2026
$60.9M
TCP5: ACTIVE SITE LABELING REAGENT FOR ACETYLTRANSFERASESU54RR020839 · NCRR · JOHNS HOPKINS UNIVERSITY · PI BOEKE, JEF D · 2004 to 2011
$27.4M
BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
Arkansas Center for Clinical and Translational ResearchUL1TR000039 · NCATS · UNIV OF ARKANSAS FOR MED SCIS · PI BECK, CORNELIA MARIE, JAMES, LAURA P · 2012 to 2014
$10.0M
Foreign - Univ. of Toronto, PI-Dr. Sachdev SidhuU01GM094588 · NIGMS · UNIVERSITY OF CHICAGO · PI KOSSIAKOFF, ANTHONY A · 2010 to 2014
$6.8M
Role of Set2 and H3 methylation in chromatin functionR01GM068088 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STRAHL, BRIAN D · 2003 to 2017
$3.4M
Center for Protein Structure and FunctionP30GM103450 · NIGMS · UNIVERSITY OF ARKANSAS AT FAYETTEVILLE · PI MILLETT, FRANCIS S · 2012 to 2014
$3.2M
Development of technology for high resolution epigenetic profiling of chromatinR01DA025755 · NIDA · UNIV OF ARKANSAS FOR MED SCIS · PI TACKETT, ALAN, TAVERNA, SEAN D. · 2008 to 2011
$1.6M
Using ChAP-MS to Study Macromolecular Chromatin Composition during TranscriptionR01GM106024 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI TACKETT, ALAN, TAVERNA, SEAN D. · 2013 to 2016
$1.2M
NCATS NIH HHS UL1 TR000039NCATS NIH HHS UL1TR000039NCRR NIH HHS U54 RR020839NIDA NIH HHS R01 DA025755NIDA NIH HHS R01DA025755NIGMS NIH HHS P20 GM103429NIGMS NIH HHS P20GM103429NIGMS NIH HHS P30 GM103450NIGMS NIH HHS P30GM103450NIGMS NIH HHS R01 GM068088NIGMS NIH HHS R01 GM106024NIGMS NIH HHS R01GM106024NIGMS NIH HHS R01GM68088NIGMS NIH HHS T32 GM007445NIGMS NIH HHS U01 GM094588NIGMS NIH HHS U01GM094588
6 · The paper itself

Abstract

Post-translational modifications of histones, such as acetylation and methylation, are differentially positioned in chromatin with respect to gene organization. For example, although histone H3 is often trimethylated on lysine 4 (H3K4me3) and acetylated on lysine 14 (H3K14ac) at active promoter regions, histone H3 lysine 36 trimethylation (H3K36me3) occurs throughout the open reading frames of transcriptionally active genes. The conserved yeast histone acetyltransferase complex, NuA3, specifically binds H3K4me3 through a plant homeodomain (PHD) finger in the Yng1 subunit, and subsequently catalyzes the acetylation of H3K14 through the histone acetyltransferase domain of Sas3, leading to transcription initiation at a subset of genes. We previously found that Ylr455w (Pdp3), an uncharacterized proline-tryptophan-tryptophan-proline (PWWP) domain-containing protein, copurifies with stable members of NuA3. Here, we employ mass-spectrometric analysis of affinity purified Pdp3, biophysical binding assays, and genetic analyses to classify NuA3 into two functionally distinct forms: NuA3a and NuA3b. Although NuA3a uses the PHD finger of Yng1 to interact with H3K4me3 at the 5'-end of open reading frames, NuA3b contains the unique member, Pdp3, which regulates an interaction between NuA3b and H3K36me3 at the transcribed regions of genes through its PWWP domain. We find that deletion of PDP3 decreases NuA3-directed transcription and results in growth defects when combined with transcription elongation mutants, suggesting NuA3b acts as a positive elongation factor. Finally, we determine that NuA3a, but not NuA3b, is synthetically lethal in combination with a deletion of the histone acetyltransferase GCN5, indicating NuA3b has a specialized role at coding regions that is independent of Gcn5 activity. Collectively, these studies define a new form of the NuA3 complex that associates with H3K36me3 to effect transcriptional elongation. MS data are available via ProteomeXchange with identifier PXD001156.

Indexed as

Protein Processing, Post-TranslationalAcetylationAmino Acid SequenceEscherichia coliHistone AcetyltransferasesHistonesMass SpectrometryMethylationMolecular Sequence DataOpen Reading FramesPeptide Chain Elongation, TranslationalPlasmidsProtein BiosynthesisProtein Structure, TertiarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsHistone AcetyltransferasesHistonesSaccharomyces cerevisiae ProteinsSAS3 protein, S cerevisiaeYng1 protein, S cerevisiae

Identifiers

PMID25104842
PMCPMC4223479

What OpenQuestion holds

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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.