Evidence map›Paper›PMID 21958861›Full record

ArticleNeuroscience2011

Regulation of POU4F3 gene expression in hair cells by 5' DNA in mice.

M Masuda, D Dulon, K Pak, L M Mullen, Y Li, L Erkman, A F Ryan

Abstract read
In one paragraph

Article in Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
1.1field-weighted citation impact, top 27% 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

45 citing papers in PubMed, 64 citations in OpenAlex.

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  6. Long-rangeProceedings of the National Academy of Sciences of the United States of America · 2024
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  11. Sufu- and Spop-mediated regulation of Gli2 is essential for the control of mammalian cochlear hair cell differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2022
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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

7 authors at 2 institutions in 2 countries.

M MasudaDepartment of Surgery/Otolaryngology, VA Medical Center and UCSD School of Medicine, 9500 Gilman Drive 0666, La Jolla, CA 92093-0666, USA.
D Dulon
K Pak
L M Mullen
Y Li
L Erkman
A F Ryan
University of California, San Diego · USUniversité de Bordeaux · FR

Funding

ENVIRONMENT INFLUENCES UPON AUDITORY DEVELOPMENTR01DC000139 · NIDCD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RYAN, ALLEN F · 1989 to 2006
$2.5M
Basic Mechanisms on Hearing Loss of Cochlear OriginI01BX001205 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI RYAN, ALLEN F. · 2013 to 2024
–
BLRD VA I01 BX001205NIDCD NIH HHS R01 DC000139
6 · The paper itself

Abstract

The POU-domain transcription POU4F3 is expressed in the sensory cells of the inner ear. Expression begins shortly after commitment to the hair cell (HC) fate, and continues throughout life. It is required for terminal HC differentiation and survival. To explore regulation of the murine Pou4f3 gene, we linked enhanced green fluorescent protein (eGFP) to 8.5 kb of genomic sequence 5' to the start codon in transgenic mice. eGFP was uniformly present in all embryonic and neonatal HCs. Expression of eGFP was also observed in developing Merkel cells and olfactory neurons as well as adult inner and vestibular HCs, mimicking the normal expression pattern of POU4F3 protein, with the exception of adult outer HCs. Apparently ectopic expression was observed in developing inner ear neurons. On a Pou4f3 null background, the transgene produced expression in embryonic HCs which faded soon after birth both in vivo and in vitro. Pou4f3 null HCs treated with caspase 3 and 9 inhibitors survived longer than untreated HCs, but still showed reduced expression of eGFP. The results suggest the existence of separate enhancers for different HC types, as well as strong autoregulation of the Pou4f3 gene. Bioinformatic analysis of four divergent mammalian species revealed three highly conserved regions within the transgene: 400 bp immediately 5' to the Pou4f3 ATG, a short sequence at -1.3 kb, and a longer region at -8.2 to -8.5 kb. The latter contained E-box motifs that bind basic helix-loop-helix (bHLH) transcription factors, including motifs activated by ATOH1. Cotransfection of HEK293 or VOT-E36 cells with ATOH1 and the transgene as a reporter enhanced eGFP expression when compared with the transgene alone. Chromatin immunoprecipitation of the three highly conserved regions revealed binding of ATOH1 to the distal-most conserved region. The results are consistent with regulation of Pou4f3 in HCs by ATOH1 at a distal enhancer.

Indexed as

Hair Cells, Auditory, InnerAnimalsBasic Helix-Loop-Helix ProteinsCell LineChromatin ImmunoprecipitationDNAE-Box ElementsGene Expression RegulationHomeodomain ProteinsMiceMice, TransgenicOligonucleotide Array Sequence AnalysisPolymerase Chain ReactionTranscription Factor Brn-3CTransfectionAtoh1 protein, mouseBasic Helix-Loop-Helix ProteinsDNAHomeodomain ProteinsPou4f3 protein, mouseTranscription Factor Brn-3C

Identifiers

PMID21958861
PMCPMC3243488
OpenAlexW2009968476

What OpenQuestion holds

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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.