Evidence map›Paper›PMID 25015561›Full record

ArticleMolecular neurobiology2015

Transcription factors with conserved binding sites near ATOH1 on the POU4F3 gene enhance the induction of cochlear hair cells.

Ryoukichi Ikeda, Kwang Pak, Eduardo Chavez, Allen F Ryan

Open access · greenAbstract read
In one paragraph

Article in Molecular neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.1field-weighted citation impact, top 15% 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

27 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. AAV-regulatedMolecular therapy. Nucleic acids · 2024
    Article
  6. AAV-mediated Gene Cocktails Enhance Supporting Cell Reprogramming and Hair Cell Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. The acquisition of positional information across the radial axis of the cochlea.Developmental dynamics : an official publication of the American Association of Anatomists · 2020
    Review
  16. Direct cellular reprogramming and inner ear regeneration.Expert opinion on biological therapy · 2019
    Review
  17. Article
  18. Article
  19. Review
  20. 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

4 authors at 2 institutions in 2 countries.

Ryoukichi Ikeda
Kwang Pak
Eduardo Chavez
Allen F Ryan
University of California, San Diego · USUniversity of California San Diego Medical Center · US

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 DC000139NIDCD NIH HHS R01DC000139
6 · The paper itself

Abstract

Overexpression of the transcription factor (TF) ATOH1 is known to induce the transformation of nonsensory cells in the organ of Corti into hair cells (HCs). Evaluating DNA 5Œ to the coding sequence of the pou4f3 gene, a target of ATOH1 in HCs, we identified in three regions containing clustered binding sites for ATOH1 and several other TFs that are expressed in developing inner ear sensory epithelia at the time of HC specification. These regions and sites are highly conserved across evolutionarily distant mammalian species. To test the hypothesis that the identified TFs act in combination to regulate the pou4f3 gene, we transfected by electroporation neonatal cochlear sensory epithelium from mice expressing green fluorescent protein (GFP) under the control of an 8.5-kb 5' pou4f3 genomic fragment. Plasmids encoding 21 TFs c-transfected with human ATOH1 (hATOH1). Cotransfection with hETV4, hNMYC, or hETS2 produced significantly more pou4f3/GFP and myosin 7A-positive nonsensory cells than hATOH1 alone. Co-transfection of hATOH1 with hHES1, hHES5, or hNEUROD1 reduced the effects of hATOH1. Chromatin immunoprecipitation (ChIP)of DNA from an inner ear cell line transfected with hNMYC,hETV4, or hETS2 revealed binding to a conserved region immediately proximal to the coding sequence. ChIP similarly revealed binding of hGATA3, hNMYC, and hTFE2 to a region several kilobases distal to the coding sequence, which we have previously shown to bind ATOH1. The results suggest that ATOH1 acts in concert with a subset of other TFs to directly regulate the pou4f3 gene and more broadly to regulate the HC phenotype.

Indexed as

AnimalsBasic Helix-Loop-Helix ProteinsBinding SitesCells, CulturedHair Cells, AuditoryHomeodomain ProteinsHumansMiceMice, Inbred CBAMice, TransgenicTranscription Factor Brn-3CTranscription FactorsATOH1 protein, humanBasic Helix-Loop-Helix ProteinsHomeodomain ProteinsPOU4F3 protein, humanTranscription Factor Brn-3CTranscription Factors

Identifiers

PMID25015561
PMCPMC4291311
OpenAlexW1975145086

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.