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Publication : Characterization of the transcriptome of nascent hair cells and identification of direct targets of the Atoh1 transcription factor.

First Author  Cai T Year  2015
Journal  J Neurosci Volume  35
Issue  14 Pages  5870-83
PubMed ID  25855195 Mgi Jnum  J:356373
Mgi Id  MGI:7762465 Doi  10.1523/JNEUROSCI.5083-14.2015
Citation  Cai T, et al. (2015) Characterization of the transcriptome of nascent hair cells and identification of direct targets of the Atoh1 transcription factor. J Neurosci 35(14):5870-83
abstractText  Hair cells are sensory receptors for the auditory and vestibular system in vertebrates. The transcription factor Atoh1 is both necessary and sufficient for the differentiation of hair cells, and is strongly upregulated during hair-cell regeneration in nonmammalian vertebrates. To identify genes involved in hair cell development and function, we performed RNA-seq profiling of purified Atoh1-expressing hair cells from the neonatal mouse cochlea. We identified >600 enriched transcripts in cochlear hair cells, of which 90% have not been previously shown to be expressed in hair cells. We identified 233 of these hair cell genes as candidates to be directly regulated by Atoh1 based on the presence of Atoh1 binding sites in their regulatory regions and by analyzing Atoh1 ChIP-seq datasets from the cerebellum and small intestine. We confirmed 10 of these genes as being direct Atoh1 targets in the cochlea by ChIP-PCR. The identification of candidate Atoh1 target genes is a first step in identifying gene regulatory networks for hair-cell development and may inform future studies on the potential role of Atoh1 in mammalian hair cell regeneration.
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