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2025
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| Online Access: | https://doi.org/10.5281/zenodo.14531704 |
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| _version_ | 1866901929719758848 |
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| author | Cheng, Yen-Fu Kempfle, Judith Chiang, Hao Tani, Kohsuke Wang, Quan Chen, Sheng-Hong Lenz, Danielle Chen, Wei-Yi Wu, Wenjin Petrillo, Marco Edge, Albert |
| author_facet | Cheng, Yen-Fu Kempfle, Judith Chiang, Hao Tani, Kohsuke Wang, Quan Chen, Sheng-Hong Lenz, Danielle Chen, Wei-Yi Wu, Wenjin Petrillo, Marco Edge, Albert |
| contents | <p>Stem cell pluripotency gene <em>Sox2</em> stimulates expression of proneural basic-helix-loop-helix transcription factor <em>Atoh1</em>. <em>Sox2</em> is necessary for the development of cochlear hair cells and binds to the <em>Atoh1</em> 3' enhancer to stimulate <em>Atoh1</em> expression. We show here that <em>Sox2</em> deletion in late embryogenesis results in the formation of extra hair cells, in contrast to the absence of hair cell development obtained after <em>Sox2</em> knockout early in gestation. <em>Sox2</em> overexpression decreased the level of Atoh1 protein despite an increase in <em>Atoh1</em> mRNA. Sox2 upregulated E3 ubiquitin ligase, <em>Huwe1</em>, by direct binding to the <em>Huwe1</em> gene. By upregulating its cognate E3 ligase, <em>Sox2</em> disrupts the positive feedback loop through which Atoh1 protein increases the expression of <em>Atoh1</em>. We conclude that <em>Sox2</em> initiates expression, while also limiting continued activity of bHLH transcription factor, Atoh1, and this inhibition represents a new mechanism for regulating the activity of this powerful initiator of hair cell development.</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_14531704 |
| institution | Zenodo |
| language | |
| publishDate | 2025 |
| publisher | Zenodo |
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| spellingShingle | Sox2 interacts with Atoh1 and Huwe1 loci to regulate Atoh1 transcription and stability during hair cell differentiation Cheng, Yen-Fu Kempfle, Judith Chiang, Hao Tani, Kohsuke Wang, Quan Chen, Sheng-Hong Lenz, Danielle Chen, Wei-Yi Wu, Wenjin Petrillo, Marco Edge, Albert Sox2 Huwe1 Atoh1 Cochlea proteasome <p>Stem cell pluripotency gene <em>Sox2</em> stimulates expression of proneural basic-helix-loop-helix transcription factor <em>Atoh1</em>. <em>Sox2</em> is necessary for the development of cochlear hair cells and binds to the <em>Atoh1</em> 3' enhancer to stimulate <em>Atoh1</em> expression. We show here that <em>Sox2</em> deletion in late embryogenesis results in the formation of extra hair cells, in contrast to the absence of hair cell development obtained after <em>Sox2</em> knockout early in gestation. <em>Sox2</em> overexpression decreased the level of Atoh1 protein despite an increase in <em>Atoh1</em> mRNA. Sox2 upregulated E3 ubiquitin ligase, <em>Huwe1</em>, by direct binding to the <em>Huwe1</em> gene. By upregulating its cognate E3 ligase, <em>Sox2</em> disrupts the positive feedback loop through which Atoh1 protein increases the expression of <em>Atoh1</em>. We conclude that <em>Sox2</em> initiates expression, while also limiting continued activity of bHLH transcription factor, Atoh1, and this inhibition represents a new mechanism for regulating the activity of this powerful initiator of hair cell development.</p> |
| title | Sox2 interacts with Atoh1 and Huwe1 loci to regulate Atoh1 transcription and stability during hair cell differentiation |
| topic | Sox2 Huwe1 Atoh1 Cochlea proteasome |
| url | https://doi.org/10.5281/zenodo.14531704 |