ArticleScientific reports2022
GFI1 regulates hair cell differentiation by acting as an off-DNA transcriptional co-activator of ATOH1, and a DNA-binding repressor.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- CASZ1 regulates the maturation of outer hair cells and is required for hearing in mice.iScience · 2026Article
- Temporally segregated functions for Gfi1 in the development and maintenance of direction selectivity in the vertebrate retina.Current biology : CB · 2026Article
- Article
- Long-rangeProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Fibrillarin homologs regulate translation in divergent cell lineages during planarian homeostasis and regeneration.The EMBO journal · 2024Article
- Reprogramming withPNAS nexus · 2024Article
- Hair Cell Regeneration: From Animals to Humans.Clinical and experimental otorhinolaryngology · 2024Review
- Expression ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Sensory cells in tunicates: insights into mechanoreceptor evolution.Frontiers in cell and developmental biology · 2024Review
- Identification of multiple transcription factor genes potentially involved in the development of electrosensoryFrontiers in cell and developmental biology · 2024Article
- Chromodomain helicase DNA binding protein 4 in cell fate decisions.Hearing research · 2023Review
- Defining developmental trajectories of prosensory cells in human inner ear organoids at single-cell resolution.Development (Cambridge, England) · 2023Article
- Future Pharmacotherapy for Sensorineural Hearing Loss by Protection and Regeneration of Auditory Hair Cells.Pharmaceutics · 2023Review
- Alternative splicing in shaping the molecular landscape of the cochlea.Frontiers in cell and developmental biology · 2023Review
- Gene therapy: an emerging therapy for hair cells regeneration in the cochlea.Frontiers in neuroscience · 2023Review
- Repurposing the lineage-determining transcription factor Atoh1 without redistributing its genomic binding sites.Frontiers in cell and developmental biology · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
GFI1 is a zinc finger transcription factor that is necessary for the differentiation and survival of hair cells in the cochlea. Deletion of Gfi1 in mice significantly reduces the expression of hundreds of hair cell genes: this is a surprising result, as GFI1 normally acts as a transcriptional repressor by recruiting histone demethylases and methyltransferases to its targets. To understand the mechanisms by which GFI1 promotes hair cell differentiation, we used CUT&RUN to identify the direct targets of GFI1 and ATOH1 in hair cells. We found that GFI1 regulates hair cell differentiation in two distinct ways-first, GFI1 and ATOH1 can bind to the same regulatory elements in hair cell genes, but while ATOH1 directly binds its target DNA motifs in many of these regions, GFI1 does not. Instead, it appears to enhance ATOH1's transcriptional activity by acting as part of a complex in which it does not directly bind DNA. Second, GFI1 can act in its more typical role as a direct, DNA-binding transcriptional repressor in hair cells; here it represses non-hair cell genes, including many neuronal genes. Together, our results illuminate the function of GFI1 in hair cell development and hair cell reprogramming strategies.
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