Evidence map›Paper›PMID 23300480›Full record

ArticlePLoS genetics2013

Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes.

Ben E Housden, Audrey Q Fu, Alena Krejci, Fred Bernard, Bettina Fischer, Simon Tavaré, Steven Russell, Sarah J Bray

Abstract read
In one paragraph

Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing 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

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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

40 citing papers in PubMed.

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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

8 authors.

Ben E HousdenDepartment of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Audrey Q Fu
Alena Krejci
Fred Bernard
Bettina Fischer
Simon Tavaré
Steven Russell
Sarah J Bray

Funding

Biotechnology and Biological Sciences Research Council BB/F00897X/1Medical Research Council G0800034
6 · The paper itself

Abstract

Dynamic activity of signaling pathways, such as Notch, is vital to achieve correct development and homeostasis. However, most studies assess output many hours or days after initiation of signaling, once the outcome has been consolidated. Here we analyze genome-wide changes in transcript levels, binding of the Notch pathway transcription factor, CSL [Suppressor of Hairless, Su(H), in Drosophila], and RNA Polymerase II (Pol II) immediately following a short pulse of Notch stimulation. A total of 154 genes showed significant differential expression (DE) over time, and their expression profiles stratified into 14 clusters based on the timing, magnitude, and direction of DE. E(spl) genes were the most rapidly upregulated, with Su(H), Pol II, and transcript levels increasing within 5-10 minutes. Other genes had a more delayed response, the timing of which was largely unaffected by more prolonged Notch activation. Neither Su(H) binding nor poised Pol II could fully explain the differences between profiles. Instead, our data indicate that regulatory interactions, driven by the early-responding E(spl)bHLH genes, are required. Proposed cross-regulatory relationships were validated in vivo and in cell culture, supporting the view that feed-forward repression by E(spl)bHLH/Hes shapes the response of late-responding genes. Based on these data, we propose a model in which Hes genes are responsible for co-ordinating the Notch response of a wide spectrum of other targets, explaining the critical functions these key regulators play in many developmental and disease contexts.

Indexed as

Basic Helix-Loop-Helix ProteinsDrosophilaDrosophila ProteinsReceptors, NotchRepressor ProteinsAnimalsBinding SitesConserved SequenceDNA-Binding ProteinsGene Expression Regulation, DevelopmentalHumansRNA Polymerase IISignal TransductionTranscriptional ActivationTranscription, GeneticBasic Helix-Loop-Helix ProteinsDNA-Binding ProteinsDrosophila ProteinsE(spl)m7-HLH protein, DrosophilaN protein, DrosophilaReceptors, NotchRepressor ProteinsRNA Polymerase II

Identifiers

PMID23300480
PMCPMC3536677

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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.