Evidence map›Paper›PMID 27875550›Full record

ArticlePloS one2016

An Alternative Approach to ChIP-Seq Normalization Enables Detection of Genome-Wide Changes in Histone H3 Lysine 27 Trimethylation upon EZH2 Inhibition.

Brian Egan, Chih-Chi Yuan, Madeleine Lisa Craske, Paul Labhart, Gulfem D Guler, David Arnott, Tobias M Maile, Jennifer Busby, Chisato Henry, Theresa K Kelly and 7 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

111 citing papers in PubMed, 162 citations in OpenAlex.

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51 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

17 authors at 3 institutions in 1 country.

Brian EganActive Motif Inc., Carlsbad, California, United States of America.ORCID http://orcid.org/0000-0002-6354-6575
Chih-Chi YuanConstellation Pharmaceuticals Inc., Cambridge, Massachusetts, United States of America.
Madeleine Lisa CraskeActive Motif Inc., Carlsbad, California, United States of America.
Paul LabhartActive Motif Inc., Carlsbad, California, United States of America.
Gulfem D GulerDepartment of Molecular Oncology, Genentech Inc., South San Francisco, California, United States of America.
David ArnottDepartment of Protein Chemistry, Genentech Inc., South San Francisco, California, United States of America.
Tobias M MaileDepartment of Protein Chemistry, Genentech Inc., South San Francisco, California, United States of America.
Jennifer BusbyConstellation Pharmaceuticals Inc., Cambridge, Massachusetts, United States of America.
Chisato HenryActive Motif Inc., Carlsbad, California, United States of America.
Theresa K KellyActive Motif Inc., Carlsbad, California, United States of America.
Charles A TindellDepartment of Molecular Oncology, Genentech Inc., South San Francisco, California, United States of America.
Suchit JhunjhunwalaDepartment of Bioinformatics, Genentech Inc., South San Francisco, California, United States of America.
Feng ZhaoConstellation Pharmaceuticals Inc., Cambridge, Massachusetts, United States of America.
Charlie HattonConstellation Pharmaceuticals Inc., Cambridge, Massachusetts, United States of America.
Barbara M BryantConstellation Pharmaceuticals Inc., Cambridge, Massachusetts, United States of America.
Marie ClassonDepartment of Molecular Oncology, Genentech Inc., South San Francisco, California, United States of America.
Patrick TrojerConstellation Pharmaceuticals Inc., Cambridge, Massachusetts, United States of America.
Constellation Pharmaceuticals (United States) · USActive Motif (United States) · USMolecular Oncology (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chromatin immunoprecipitation and DNA sequencing (ChIP-seq) has been instrumental in inferring the roles of histone post-translational modifications in the regulation of transcription, chromatin compaction and other cellular processes that require modulation of chromatin structure. However, analysis of ChIP-seq data is challenging when the manipulation of a chromatin-modifying enzyme significantly affects global levels of histone post-translational modifications. For example, small molecule inhibition of the methyltransferase EZH2 reduces global levels of histone H3 lysine 27 trimethylation (H3K27me3). However, standard ChIP-seq normalization and analysis methods fail to detect a decrease upon EZH2 inhibitor treatment. We overcome this challenge by employing an alternative normalization approach that is based on the addition of Drosophila melanogaster chromatin and a D. melanogaster-specific antibody into standard ChIP reactions. Specifically, the use of an antibody that exclusively recognizes the D. melanogaster histone variant H2Av enables precipitation of D. melanogaster chromatin as a minor fraction of the total ChIP DNA. The D. melanogaster ChIP-seq tags are used to normalize the human ChIP-seq data from DMSO and EZH2 inhibitor-treated samples. Employing this strategy, a substantial reduction in H3K27me3 signal is now observed in ChIP-seq data from EZH2 inhibitor treated samples.

Indexed as

AnimalsChromatin ImmunoprecipitationDrosophila melanogasterDrosophila ProteinsEnhancer of Zeste Homolog 2 ProteinEnzyme InhibitorsGenome-Wide Association StudyHistonesHumansMethylationSequence Analysis, DNADrosophila ProteinsEnhancer of Zeste Homolog 2 ProteinEnzyme InhibitorsHistones

Identifiers

PMID27875550
PMCPMC5119738
OpenAlexW2553076365

What OpenQuestion holds

Textmetadata
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.