ArticleNucleic acids research2020
Dynamic changes in cis-regulatory occupancy by Six1 and its cooperative interactions with distinct cofactors drive lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
- SIX1 branchio-oto-renal syndrome variants have different effects on embryonic craniofacial gene expression and cartilage formation.Development (Cambridge, England) · 2026Article
- Active chromatin marks and up-regulation of FOXC1 in uterine epithelial cells demarcate the onset of reproductive decline in aging females.NAR molecular medicine · 2025Article
- Targets of the transcription factor Six1 identify previously unreported candidate deafness genes.Development (Cambridge, England) · 2025Article
- Multi-omic analysis of the ciliogenic transcription factorbioRxiv : the preprint server for biology · 2025Article
- Single-cell atlas comparison across vertebrates reveals auditory cell evolution and mechanisms for hair cell regeneration.Communications biology · 2024Article
- Article
- AAV-mediated Gene Cocktails Enhance Supporting Cell Reprogramming and Hair Cell Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Shared features in ear and kidney development - implications for oto-renal syndromes.Disease models & mechanisms · 2024Article
- PBX1: a TALE of two seasons-key roles during development and in cancer.Frontiers in cell and developmental biology · 2024Review
- Altered binding affinity of SIX1-Q177R correlates with enhanced WNT5A and WNT pathway effector expression in Wilms tumor.Disease models & mechanisms · 2023Article
- Transcriptomic analysis reveals the role of SIX1 in mouse cranial neural crest patterning and bone development.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Article
- SIX1 and EWS/FLI1 co-regulate an anti-metastatic gene network in Ewing Sarcoma.Nature communications · 2023Article
- Accelerated Evolution Analysis Uncovers PKNOX2 as a Key Transcription Factor in the Mammalian Cochlea.Molecular biology and evolution · 2023Article
- The evolution of the various structures required for hearing inIBRO neuroscience reports · 2023Article
- Early Steps towards Hearing: Placodes and Sensory Development.International journal of molecular sciences · 2023Review
- EctomesenchymalFrontiers in genetics · 2023Article
- Molecular mechanisms governing development of the hindbrain choroid plexus and auditory projection: A validation of the seminal observations of Wilhelm His.IBRO neuroscience reports · 2022Review
- The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and REST-binding sequences to maintain nephron progenitor identity.Nucleic acids research · 2022Article
- Merkel Cell Carcinoma Sensitivity to EZH2 Inhibition Is Mediated by SIX1 Derepression.The Journal of investigative dermatology · 2022Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The transcription factor Six1 is essential for induction of sensory cell fate and formation of auditory sensory epithelium, but how it activates gene expression programs to generate distinct cell-types remains unknown. Here, we perform genome-wide characterization of Six1 binding at different stages of auditory sensory epithelium development and find that Six1-binding to cis-regulatory elements changes dramatically at cell-state transitions. Intriguingly, Six1 pre-occupies enhancers of cell-type-specific regulators and effectors before their expression. We demonstrate in-vivo cell-type-specific activity of Six1-bound novel enhancers of Pbx1, Fgf8, Dusp6, Vangl2, the hair-cell master regulator Atoh1 and a cascade of Atoh1's downstream factors, including Pou4f3 and Gfi1. A subset of Six1-bound sites carry consensus-sequences for its downstream factors, including Atoh1, Gfi1, Pou4f3, Gata3 and Pbx1, all of which physically interact with Six1. Motif analysis identifies RFX/X-box as one of the most significantly enriched motifs in Six1-bound sites, and we demonstrate that Six1-RFX proteins cooperatively regulate gene expression through binding to SIX:RFX-motifs. Six1 targets a wide range of hair-bundle regulators and late Six1 deletion disrupts hair-bundle polarity. This study provides a mechanistic understanding of how Six1 cooperates with distinct cofactors in feedforward loops to control lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium.
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