The Repression of Atoh1 by Neurogenin1 during Inner Ear Development

Frontiers in Molecular Neuroscience
Héctor GálvezGina Abelló

Abstract

Atonal homolog 1 (Atoh1) and Neurogenin1 (Neurog1) are basic Helix-Loop-Helix (bHLH) transcription factors crucial for the generation of hair cells (HCs) and neurons in the inner ear. Both genes are induced early in development, but the expression of Atoh1 is counteracted by Neurog1. As a result, HC development is prevented during neurogenesis. This work aimed at understanding the molecular basis of this interaction. Atoh1 regulation depends on a 3'Atoh1-enhancer that is the site for Atoh1 autoregulation. Reporter assays on chick embryos and P19 cells show that Neurog1 hampers the autoactivation of Atoh1, the effect being cell autonomous and independent on Notch activity. Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-Seq) analysis shows that the region B of the 3'Atoh1-enhancer is accessible during development and sufficient for both activation and repression. Neurog1 requires the regions flanking the class A E-box to show its repressor effect, however, it does not require binding to DNA for Atoh1 repression. This depends on the dimerization domains Helix-1 and Helix-2 and the reduction of Atoh1 protein levels. The results point towards the acceleration of Atoh1 mRNA degradation as the potenti...Continue Reading

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Citations

Jun 23, 2019·Scientific Reports·Brent A WilkersonOlivia Bermingham-McDonogh
Jan 27, 2019·Hearing Research·Bradley J Walters, Brandon C Cox
Mar 27, 2021·Stem Cell Reports·Dunia Abdul-AzizAlbert S B Edge
Sep 3, 2021·The Journal of Investigative Dermatology·Paul W HarmsArul M Chinnaiyan

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Methods Mentioned

BETA
Assay
PCR
Transfection
immunoprecipitation
ATAC-Seq
immunoprecipitations
transgenic

Software Mentioned

Bowtie2
Quantity One
SAINTexpress

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