Evidence map›Paper›PMID 24269917›Full record

ArticleNeurobiology of disease2014

Genome-wide approaches reveal EGR1-controlled regulatory networks associated with neurodegeneration.

Radosveta Koldamova, Jonathan Schug, Martina Lefterova, Andrea A Cronican, Nicholas F Fitz, Faith A Davenport, Alexis Carter, Emilie L Castranio, Iliya Lefterov

Open access · greenAbstract read
In one paragraph

Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

51 citing papers in PubMed, 72 citations in OpenAlex.

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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

9 authors at 3 institutions in 1 country.

Radosveta KoldamovaDepartment of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: radak@pitt.edu.
Jonathan SchugInstitute for Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA; Functional Genomics Core, Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Martina LefterovaDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Andrea A CronicanDepartment of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Nicholas F FitzDepartment of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Faith A DavenportDepartment of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Alexis CarterDepartment of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Emilie L CastranioDepartment of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Iliya LefterovDepartment of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: iliyal@pitt.edu.
University of Pittsburgh · USStanford University · USUniversity of Pennsylvania · US

Funding

Genome wide analysis of LXR binding - metabolic and epigenetic regulation in ADR01AG037919 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEFTEROV, ILIYA, SCHUG, JONATHAN · 2012 to 2016
$2.4M
LXR and human ApoE isoform effects on AD phenotype: in vitro and in vivo modelsR01AG037481 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KOLDAMOVA, RADOSVETA · 2011 to 2015
$1.8M
Epigenomic impact of diet and toxicant exposure in Alzheimers disease etiologyR21ES021243 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BARCHOWSKY, AARON, LEFTEROV, ILIYA · 2012 to 2013
$468k
Role of LXR and ABCA1 in Abeta Aggregation and ToxicityF32AG034031 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FITZ, NICHOLAS FRANCIS · 2009 to 2012
$152k
NIA NIH HHS F32 AG034031NIA NIH HHS R01 AG037481NIA NIH HHS R01 AG037919NIEHS NIH HHS R21 ES021243
6 · The paper itself

Abstract

Early growth response gene 1 (Egr1) is a member of the immediate early gene (IEG) family of transcription factors and plays a role in memory formation. To identify EGR1 target genes in brain of Alzheimer's disease (AD) model mice - APP23, we applied chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq). Functional annotation of genes associated with EGR1 binding revealed a set of related networks including synaptic vesicle transport, clathrin-mediated endocytosis (CME), intracellular membrane fusion and transmission of signals elicited by Ca(2+) influx. EGR1 binding is associated with significant enrichment of activating chromatin marks and appears enriched near genes that are up-regulated in the brains of APP23 mice. Among the putative EGR1 targets identified and validated in this study are genes related to synaptic plasticity and transport of proteins, such as Arc, Grin1, Syn2, Vamp2 and Stx6, and genes implicated in AD such as Picalm, Psen2 and App. We also demonstrate a potential regulatory link between EGR1 and its newly identified targets in vivo, since conditions that up-regulate Egr1 levels in brain, such as a spatial memory test, also lead to increased expression of the targets. On the other hand, protein levels of EGR1 and ARC, SYN2, STX6 and PICALM are significantly lower in the brain of adult APP mice than in age-matched wild type animals. The results of this study suggest that EGR1 regulates the expression of genes involved in CME, vesicular transport and synaptic transmission that may be critical for AD pathogenesis.

Indexed as

GenomeAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsChlorocebus aethiopsChromatin ImmunoprecipitationCOS CellsDisease Models, AnimalEarly Growth Response Protein 1EndocytosisGene Regulatory NetworksGreen Fluorescent ProteinsMiceMice, Inbred C57BLMice, TransgenicNerve DegenerationAmyloid beta-Protein PrecursorEarly Growth Response Protein 1Egr1 protein, mouseGreen Fluorescent ProteinsNerve Tissue ProteinsAlzheimer's diseaseAnimal modelBrainChIP-seqEgr1Histone modifications

Identifiers

PMID24269917
PMCPMC3939039
OpenAlexW2040193459

What OpenQuestion holds

Textmetadata
LicenceTDM
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.