Evidence map›Paper›PMID 25051175›Full record

ArticlePloS one2014

Histone acetyltransferase p300 mediates histone acetylation of PS1 and BACE1 in a cellular model of Alzheimer's disease.

Xi Lu, Yushuang Deng, Daohai Yu, Huiming Cao, Li Wang, Li Liu, Caijia Yu, Yuping Zhang, Xiuming Guo, Gang Yu

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

44 citing papers in PubMed, 96 citations in OpenAlex.

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  17. Protective effect ofBiomedical reports · 2023
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  19. Tip60's Novel RNA-Binding Function Modulates Alternative Splicing of Pre-mRNA Targets Implicated in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
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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

10 authors at 6 institutions in 2 countries.

Xi LuDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China; Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
Yushuang DengDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China; Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
Daohai YuDepartment of Clinical Sciences, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
Huiming CaoDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China; Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
Li WangDepartment of Bio-therapy & Hemato-oncology, Chingqing Cancer Institute, Chongqing, P.R. China.
Li LiuDepartment of Neurology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, P.R. China.
Caijia YuGenetics and Molecular Biology, Northwestern University, Evanston, Illinois, United States of America.
Yuping ZhangDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
Xiuming GuoDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
Gang YuDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
First Affiliated Hospital of Chongqing Medical University · CNChongqing Medical University · CNChongqing Cancer Hospital · CNFirst People's Hospital of Chongqing · CNNorthwestern University · USTemple University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epigenetic modifications, particularly histone acetylation, have been implicated in Alzheimer's disease (AD). While previous studies have suggested that histone hypoacetylation may regulate the expression of genes associated with memory and learning in AD, little is known about histone regulation of AD-related genes such as Presenilin 1(PS1) and beta-site amyloid precursor protein cleaving enzyme 1(BACE1). By utilizing neuroblastoma N2a cells transfected with Swedish mutated human amyloid precursor protein (APP) (N2a/APPswe) and wild-type APP (N2a/APPwt) as cellular models of AD, we examined the alterations of histone acetylation at the promoter regions of PS1 and BACE1 in these cells. Our results revealed that histone H3 acetylation in PS1 and BACE1 promoters is markedly increased in N2a/APPswe cells when compared to N2a/APPwt cells and control cells (vector-transfected), respectively, causing the elevated expression of PS1 and BACE1. In addition, expression of histone acetyltransferase (HAT) adenoviral E1A-associated 300-kDa protein (p300) is dramatically enhanced in N2a/APPswe cells compared to N2a/APPwt and control cells. We have further demonstrated the direct binding of p300 protein to the PS1 and BACE1 promoters in N2a/APPswe cells. The expression levels of H3 acetylation of the PS1 and BACE1 promoters and p300 protein, however, were found to be not significantly different in N2a/APPwt cells when compared to controls in our studies. Furthermore, curcumin, a natural selective inhibitor of p300 in HATs, significantly suppressed the expression of PS1 and BACE1 through inhibition of H3 acetylation in their promoter regions in N2a/APPswe cells. These findings indicated that histone acetyltransferase p300 plays a critical role in controlling the expression of AD-related genes through regulating the acetylation of their promoter regions, suggesting that p300 may represent a novel potential therapeutic target for AD.

Indexed as

AcetylationAlzheimer DiseaseAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesCell LineE1A-Associated p300 ProteinEpigenesis, GeneticGene Expression RegulationHistonesHumansMiceNeuronsPresenilin-1Promoter Regions, GeneticAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBace1 protein, mouseE1A-Associated p300 ProteinEp300 protein, mouseHistonesPresenilin-1

Identifiers

PMID25051175
PMCPMC4106886
OpenAlexW2069696610

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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.