Evidence map›Paper›PMID 32859943›Full record

ArticleCommunications biology2020

Coordinated regulation of Rel expression by MAP3K4, CBP, and HDAC6 controls phenotypic switching.

Noha Ahmed Mohammed Shendy, Deepthi Raghu, Sujoy Roy, Charles Hamilton Perry, Adiba Safi, Miguel Ramos Branco, Ramin Homayouni, Amy Noel Abell

Abstract read
In one paragraph

Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

8 authors.

Noha Ahmed Mohammed ShendyDepartment of Biological Sciences, University of Memphis, Memphis, TN, 38152, USA.ORCID http://orcid.org/0000-0002-4765-6774
Deepthi RaghuDepartment of Biological Sciences, University of Memphis, Memphis, TN, 38152, USA.
Sujoy RoyDepartment of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI, 48309-4482, USA.
Charles Hamilton PerryDepartment of Biological Sciences, University of Memphis, Memphis, TN, 38152, USA.
Adiba SafiDepartment of Biological Sciences, University of Memphis, Memphis, TN, 38152, USA.
Miguel Ramos BrancoCentre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, London, E1 2AT, UK.ORCID http://orcid.org/0000-0001-9447-1548
Ramin HomayouniDepartment of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI, 48309-4482, USA.ORCID http://orcid.org/0000-0003-0186-5076
Amy Noel AbellDepartment of Biological Sciences, University of Memphis, Memphis, TN, 38152, USA. anabell@memphis.edu.ORCID http://orcid.org/0000-0003-0604-7566

Funding

COORDINATE REGULATION BY MAP3K4 OF EPIGENETIC MODIFIERS CONTROLLING EMTR01GM116903 · NIGMS · UNIVERSITY OF MEMPHIS · PI ABELL, AMY N · 2015 to 2019
$1.5M
NIGMS NIH HHS GM116903NIGMS NIH HHS R01 GM116903
6 · The paper itself

Abstract

Coordinated gene expression is required for phenotypic switching between epithelial and mesenchymal phenotypes during normal development and in disease states. Trophoblast stem (TS) cells undergo epithelial-mesenchymal transition (EMT) during implantation and placentation. Mechanisms coordinating gene expression during these processes are poorly understood. We have previously demonstrated that MAP3K4-regulated chromatin modifiers CBP and HDAC6 each regulate thousands of genes during EMT in TS cells. Here we show that CBP and HDAC6 coordinate expression of only 183 genes predicted to be critical regulators of phenotypic switching. The highest-ranking co-regulated gene is the NF-κB family member Rel. Although NF-κB is primarily regulated post-transcriptionally, CBP and HDAC6 control Rel transcript levels by binding Rel regulatory regions and controlling histone acetylation. REL re-expression in mesenchymal-like TS cells induces a mesenchymal-epithelial transition. Importantly, REL forms a feedback loop, blocking HDAC6 expression and nuclear localization. Together, our work defines a developmental program coordinating phenotypic switching.

Indexed as

Gene Expression RegulationPhenotypeAnimalsEpithelial CellsEpithelial-Mesenchymal TransitionFemaleHistone Deacetylase 6HumansMaleMAP Kinase Kinase Kinase 4MiceModels, BiologicalOncogene Proteins v-relPeptide FragmentsProtein TransportProto-Oncogene Proteins c-metbone sialoprotein (35-62), humanHDAC6 protein, humanHistone Deacetylase 6MAP3K4 protein, humanMAP Kinase Kinase Kinase 4MET protein, humanOncogene Proteins v-relPeptide FragmentsProto-Oncogene Proteins c-metSialoglycoproteinsTranscription Factors

Identifiers

PMID32859943
PMCPMC7455715

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.