Evidence map›Paper›PMID 25680960›Full record

ArticleMolecular & cellular proteomics : MCP2015

Mass spectrometric quantification of histone post-translational modifications by a hybrid chemical labeling method.

Tobias M Maile, Anita Izrael-Tomasevic, Tommy Cheung, Gulfem D Guler, Charles Tindell, Alexandre Masselot, Jun Liang, Feng Zhao, Patrick Trojer, Marie Classon and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

59 citing papers in PubMed, 121 citations in OpenAlex.

  1. Article
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  3. Enhanced plant bottom-up histone proteomics.Journal of experimental botany · 2026
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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

11 authors at 4 institutions in 2 countries.

Tobias M MaileFrom the ‡Protein Chemistry Department, Genentech Inc., South San Francisco, California 94080;
Anita Izrael-TomasevicFrom the ‡Protein Chemistry Department, Genentech Inc., South San Francisco, California 94080;
Tommy CheungFrom the ‡Protein Chemistry Department, Genentech Inc., South San Francisco, California 94080;
Gulfem D Guler§Cancer Targets Department, Genentech, Inc., South San Francisco, California 94080;
Charles Tindell§Cancer Targets Department, Genentech, Inc., South San Francisco, California 94080;
Alexandre Masselot¶Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, California 94080;
Jun Liang‖Discovery Chemistry Department, Genentech, Inc., South San Francisco, California 94080;
Feng Zhao**Biology Department, Constellation Pharmaceuticals, Inc., Cambridge, Massachusetts 02142.
Patrick Trojer**Biology Department, Constellation Pharmaceuticals, Inc., Cambridge, Massachusetts 02142.
Marie Classon§Cancer Targets Department, Genentech, Inc., South San Francisco, California 94080;
David ArnottFrom the ‡Protein Chemistry Department, Genentech Inc., South San Francisco, California 94080; arnott@gene.com.
PDL BioPharma (United States) · USTarget (United States) · USConstellation Pharmaceuticals (United States) · USDiscovery Centre · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mass spectrometry is a powerful alternative to antibody-based methods for the analysis of histone post-translational modifications (marks). A key development in this approach was the deliberate propionylation of histones to improve sequence coverage across the lysine-rich and hydrophilic tails that bear most modifications. Several marks continue to be problematic however, particularly di- and tri-methylated lysine 4 of histone H3 which we found to be subject to substantial and selective losses during sample preparation and liquid chromatography-mass spectrometry. We developed a new method employing a "one-pot" hybrid chemical derivatization of histones, whereby an initial conversion of free lysines to their propionylated forms under mild aqueous conditions is followed by trypsin digestion and labeling of new peptide N termini with phenyl isocyanate. High resolution mass spectrometry was used to collect qualitative and quantitative data, and a novel web-based software application (Fishtones) was developed for viewing and quantifying histone marks in the resulting data sets. Recoveries of 53 methyl, acetyl, and phosphoryl marks on histone H3.1 were improved by an average of threefold overall, and over 50-fold for H3K4 di- and tri-methyl marks. The power of this workflow for epigenetic research and drug discovery was demonstrated by measuring quantitative changes in H3K4 trimethylation induced by small molecule inhibitors of lysine demethylases and siRNA knockdown of epigenetic modifiers ASH2L and WDR5.

Indexed as

Protein Processing, Post-TranslationalChromatography, LiquidGene Knockdown TechniquesHEK293 CellsHeLa CellsHistone DemethylasesHistonesHumansLysineMass SpectrometryMethylationPeptidesPropionatesReference StandardsRNA, Small InterferingStaining and LabelingHistone DemethylasesHistonesLysinePeptidesPropionatespropionic acidRNA, Small InterferingTrypsin

Identifiers

PMID25680960
PMCPMC4390259
OpenAlexW2156806661

What OpenQuestion holds

Textmetadata
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.