Evidence map›Paper›PMID 26549458›Full record

ArticleCell reports2015

Histone Deacetylases Positively Regulate Transcription through the Elongation Machinery.

Celeste B Greer, Yoshiaki Tanaka, Yoon Jung Kim, Peng Xie, Michael Q Zhang, In-Hyun Park, Tae Hoon Kim

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed
5.3field-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

117 citing papers in PubMed, 175 citations in OpenAlex.

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57 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

7 authors at 3 institutions in 1 country.

Celeste B GreerDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
Yoshiaki TanakaDepartment of Genetics and Stem Cell Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Yoon Jung KimDepartment of Biological Sciences and Center for Systems Biology, The University of Texas at Dallas, Richardson, TX 75080, USA.
Peng XieDepartment of Biological Sciences and Center for Systems Biology, The University of Texas at Dallas, Richardson, TX 75080, USA.
Michael Q ZhangDepartment of Biological Sciences and Center for Systems Biology, The University of Texas at Dallas, Richardson, TX 75080, USA.
In-Hyun ParkDepartment of Genetics and Stem Cell Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Tae Hoon KimDepartment of Biological Sciences and Center for Systems Biology, The University of Texas at Dallas, Richardson, TX 75080, USA. Electronic address: genome@utdallas.edu.
Yale University · USCenter for Systems Biology · USThe University of Texas at Dallas · US

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
Project 3: Effect of Age and Longevity Genes on Epigenomic MechanismsP01GM099130 · NIGMS · STANFORD UNIVERSITY · PI WEISSMAN, SHERMAN MORTON · 2011 to 2015
$11.4M
INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDT32GM007324 · NIGMS · YALE UNIVERSITY · PI BENNETT, ANTON M · 1987 to 2022
$6.2M
Cell-based genomic analysis of molecular pathology in Mouse Models of Rett SyndromeR01MH102616 · NIMH · COLD SPRING HARBOR LABORATORY · PI HUANG, Z JOSH · 2014 to 2018
$3.8M
Analysis of Higher Order Chromatin Structures in Normal and Cancer EpigenomesR01CA140485 · NCI · YALE UNIVERSITY · PI KIM, TAE HOON · 2010 to 2014
$1.6M
Investigation of the function of methylated DNA binding protein in reprogrammingR01GM111667 · NIGMS · YALE UNIVERSITY · PI PARK, IN-HYUN · 2014 to 2018
$1.6M
Nuclear, Genomic and Molecular Regulation of Type I Interferon TranscriptionR21AI107067 · NIAID · YALE UNIVERSITY · PI KIM, TAE HOON · 2013 to 2014
$426k
NCI NIH HHS P30 CA016359NCI NIH HHS R01 CA140485NCI NIH HHS R01CA140485NIAID NIH HHS R21 AI107067NIAID NIH HHS R21AI107067NIGMS NIH HHS GM007324NIGMS NIH HHS GM0099130-01NIGMS NIH HHS GM111667-01NIGMS NIH HHS P01 GM099130NIGMS NIH HHS R01 GM111667NIGMS NIH HHS T32 GM007324NIMH NIH HHS R01 MH102616
6 · The paper itself

Abstract

Transcription elongation regulates the expression of many genes, including oncogenes. Histone deacetylase (HDAC) inhibitors (HDACIs) block elongation, suggesting that HDACs are involved in gene activation. To understand this, we analyzed nascent transcription and elongation factor binding genome-wide after perturbation of elongation with small molecule inhibitors. We found that HDACI-mediated repression requires heat shock protein 90 (HSP90) activity. HDACIs promote the association of RNA polymerase II (RNAP2) and negative elongation factor (NELF), a complex stabilized by HSP90, at the same genomic sites. Additionally, HDACIs redistribute bromodomain-containing protein 4 (BRD4), a key elongation factor involved in enhancer activity. BRD4 binds to newly acetylated sites, and its occupancy at promoters and enhancers is reduced. Furthermore, HDACIs reduce enhancer activity, as measured by enhancer RNA production. Therefore, HDACs are required for limiting acetylation in gene bodies and intergenic regions. This facilitates the binding of elongation factors to properly acetylated promoters and enhancers for efficient elongation.

Indexed as

Epigenesis, GeneticTranscription Elongation, GeneticAcetylationBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorHistone Deacetylase InhibitorsHistone DeacetylasesHSP90 Heat-Shock ProteinsHumansKineticsNuclear ProteinsProtein BindingProtein Processing, Post-TranslationalRNA Polymerase IITranscription FactorsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsHistone Deacetylase InhibitorsHistone DeacetylasesHSP90 Heat-Shock ProteinsNuclear ProteinsRNA Polymerase IITranscription Factors

Identifiers

PMID26549458
PMCPMC4934896
OpenAlexW2108078777

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.