Evidence map›Paper›PMID 11564889›Full record

ArticleMolecular and cellular biology2001

The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression.

B P Ashburner, S D Westerheide, A S Baldwin

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

Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 332 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
332citing papers in PubMed, 3 pooled it
14.1field-weighted citation impact, top 1% 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

332 citing papers in PubMed, 3 syntheses or guidelines pooled it, 729 citations in OpenAlex.

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272 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

3 authors at 2 institutions in 2 countries.

B P AshburnerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
S D Westerheide
A S Baldwin
Segeberger Kliniken · DEUNC Lineberger Comprehensive Cancer Center

Funding

Unexpected Nucleosomal Functions for the IKKsR37AI035098 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BALDWIN, ALBERT SIDNEY · 2004 to 2013
$3.2M
Unusual Regulation of the NF-kappaB/IKK Pathway by RasR01CA073756 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BALDWIN, ALBERT SIDNEY · 1998 to 2014
$3.2M
TNF SIGNALING--ACTIVATION OF NF-KB AND GENE EXPRESSIONR01AI035098 · NIAID · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI BALDWIN, ALBERT SIDNEY · 1994 to 2003
$981k
NCI NIH HHS CA 73756NCI NIH HHS R01 CA073756NIAID NIH HHS AI35098NIAID NIH HHS R01 AI035098NIAID NIH HHS R37 AI035098
6 · The paper itself

Abstract

Regulation of NF-kappaB transactivation function is controlled at several levels, including interactions with coactivator proteins. Here we show that the transactivation function of NF-kappaB is also regulated through interaction of the p65 (RelA) subunit with histone deacetylase (HDAC) corepressor proteins. Our results show that inhibition of HDAC activity with trichostatin A (TSA) results in an increase in both basal and induced expression of an integrated NF-kappaB-dependent reporter gene. Chromatin immunoprecipitation (ChIP) assays show that TSA treatment causes hyperacetylation of the wild-type integrated NF-kappaB-dependent reporter but not of a mutant version in which the NF-kappaB binding sites were mutated. Expression of HDAC1 and HDAC2 repressed tumor necrosis factor (TNF)-induced NF-kappaB-dependent gene expression. Consistent with this, we show that HDAC1 and HDAC2 target NF-kappaB through a direct association of HDAC1 with the Rel homology domain of p65. HDAC2 does not interact with NF-kappaB directly but can regulate NF-kappaB activity through its association with HDAC1. Finally, we show that inhibition of HDAC activity with TSA causes an increase in both basal and TNF-induced expression of the NF-kappaB-regulated interleukin-8 (IL-8) gene. Similar to the wild-type integrated NF-kappaB-dependent reporter, ChIP assays showed that TSA treatment resulted in hyperacetylation of the IL-8 promoter. These data indicate that the transactivation function of NF-kappaB is regulated in part through its association with HDAC corepressor proteins. Moreover, it suggests that the association of NF-kappaB with the HDAC1 and HDAC2 corepressor proteins functions to repress expression of NF-kappaB-regulated genes as well as to control the induced level of expression of these genes.

Indexed as

Down-RegulationGene Expression Regulation, EnzymologicRepressor Proteins3T3 CellsAcetylationAnimalsBinding SitesBlotting, NorthernBlotting, WesternCell LineChromatinCOS CellsEnzyme InhibitorsHeLa CellsHistone Deacetylase 1Histone Deacetylase 2ChromatinEnzyme InhibitorsHDAC1 protein, humanHdac2 protein, mouseHistone Deacetylase 1Histone Deacetylase 2Histone DeacetylasesHydroxamic AcidsLuciferasesNF-kappa BRepressor ProteinsTranscription Factor RelAtrichostatin A

Identifiers

PMID11564889
PMCPMC99882
OpenAlexW2144929276

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.