Ontology highlight
ABSTRACT:
PROVIDER: PRJNA256313 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tightly controlled gene expression orchestrated by the transcription factor p63 during epithelial differentiation is important for development of epithelial-related structures such as epidermis, limb and craniofacial regions. How p63 regulates spatial and temporal expression of its target genes during these developmental processes is however not yet clear. By epigenomics profiling in stem cells established from one of these epithelial structures, the epidermis, we provide a global map of p63-bound regulatory elements that are categorized as single enhancers and clustered enhancers during epidermal differentiation. Transcriptomics analysis shows dynamic gene expression patterns during epidermal differentiation that correlates with the activity of p63-bound enhancers rather than with p63 binding itself. Only a subset of p63-bound enhancers is active in epidermal stem cells, and inactive p63-bound enhancers appear to function in gene regulation during the development of other epithelial tissues. Our data suggest a paradigm that p63 bookmarks genomic loci during the commitment of the epithelial lineage and regulates gene expression in different epithelial tissues through tissue-specific active enhancers. The catalogue of differentially expressed epidermal genes including non-coding RNAs and epithelial enhancers reported here provides a rich resource for studies of epithelial development and related diseases. Comparison of gene expression at different stages of keratinocyte differentiation
2015-05-01 | E-GEOD-59822 | biostudies-arrayexpress
Project description:Tightly controlled gene expression orchestrated by the transcription factor p63 during epithelial differentiation is important for development of epithelial-related structures such as epidermis, limb and craniofacial regions. How p63 regulates spatial and temporal expression of its target genes during these developmental processes is however not yet clear. By epigenomics profiling in stem cells established from one of these epithelial structures, the epidermis, we provide a global map of p63-bound regulatory elements that are categorized as single enhancers and clustered enhancers during epidermal differentiation. Transcriptomics analysis shows dynamic gene expression patterns during epidermal differentiation that correlates with the activity of p63-bound enhancers rather than with p63 binding itself. Only a subset of p63-bound enhancers is active in epidermal stem cells, and inactive p63-bound enhancers appear to function in gene regulation during the development of other epithelial tissues. Our data suggest a paradigm that p63 bookmarks genomic loci during the commitment of the epithelial lineage and regulates gene expression in different epithelial tissues through tissue-specific active enhancers. The catalogue of differentially expressed epidermal genes including non-coding RNAs and epithelial enhancers reported here provides a rich resource for studies of epithelial development and related diseases. Different stages of keratinocyte differentiation
2015-05-01 | E-GEOD-59824 | biostudies-arrayexpress
Project description:Tightly controlled gene expression orchestrated by the transcription factor p63 during epithelial differentiation is important for development of epithelial-related structures such as epidermis, limb and craniofacial regions. How p63 regulates spatial and temporal expression of its target genes during these developmental processes is however not yet clear. By epigenomics profiling in stem cells established from one of these epithelial structures, the epidermis, we provide a global map of p63-bound regulatory elements that are categorized as single enhancers and clustered enhancers during epidermal differentiation. Transcriptomics analysis shows dynamic gene expression patterns during epidermal differentiation that correlates with the activity of p63-bound enhancers rather than with p63 binding itself. Only a subset of p63-bound enhancers is active in epidermal stem cells, and inactive p63-bound enhancers appear to function in gene regulation during the development of other epithelial tissues. Our data suggest a paradigm that p63 bookmarks genomic loci during the commitment of the epithelial lineage and regulates gene expression in different epithelial tissues through tissue-specific active enhancers. The catalogue of differentially expressed epidermal genes including non-coding RNAs and epithelial enhancers reported here provides a rich resource for studies of epithelial development and related diseases.
2015-05-01 | GSE59824 | GEO
Project description:Tightly controlled gene expression orchestrated by the transcription factor p63 during epithelial differentiation is important for development of epithelial-related structures such as epidermis, limb and craniofacial regions. How p63 regulates spatial and temporal expression of its target genes during these developmental processes is however not yet clear. By epigenomics profiling in stem cells established from one of these epithelial structures, the epidermis, we provide a global map of p63-bound regulatory elements that are categorized as single enhancers and clustered enhancers during epidermal differentiation. Transcriptomics analysis shows dynamic gene expression patterns during epidermal differentiation that correlates with the activity of p63-bound enhancers rather than with p63 binding itself. Only a subset of p63-bound enhancers is active in epidermal stem cells, and inactive p63-bound enhancers appear to function in gene regulation during the development of other epithelial tissues. Our data suggest a paradigm that p63 bookmarks genomic loci during the commitment of the epithelial lineage and regulates gene expression in different epithelial tissues through tissue-specific active enhancers. The catalogue of differentially expressed epidermal genes including non-coding RNAs and epithelial enhancers reported here provides a rich resource for studies of epithelial development and related diseases.
2015-05-01 | GSE59822 | GEO
Project description:Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dynamic enhancers (RNA-Seq)
| PRJNA256310 | ENA
Project description:Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dynamic enhancers (ChIP-Seq)
| PRJNA256315 | ENA
Project description:<p>Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with Ectrodactyly Ectodermal Dysplasia Cleft Lip/Palate (EEC) syndrome. Underlying molecular mechanism of these mutations however remain unclear. Here we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and by unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify an unreported disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.</p>
| phs001737 | dbGaP
Project description:The transcription factor p63 is a master regulator of ectoderm development essential for epidermal specification. Although previous studies have highlighted the role of p63 triggering the epidermal transcriptomic program, its precise mechanism of target gene regulation in the complex context of a developing embryo remains poorly understood. Here, we used zebrafish embryos to analyze in vivo how p63 regulates the expression of its target genes during development. We generated tp63-knock-out mutants that recapitulate human phenotypes and show down-regulated epidermal gene expression. Following p63-binding dynamics during development, we found two distinct functions clearly separated in space and time. During early development, p63 binds enhancers associated to neural genes, where it limits Sox3 binding and reduces the expression of these neural genes. Indeed, we show that p63 and Sox3 are co-expressed in the neural plate border. Later in development, p63 binds enhancers associated to epidermal genes and promotes their expression, acting as a pioneer factor, as it binds to non-accessible chromatin and is required for its opening. Therefore, our results suggest that p63 is an important regulator of cell fate decisions during ectoderm specification, promoting the epidermal fate and inhibiting the neural program.
2019-06-06 | GSE123058 | GEO
Project description:The transcription factor p63 is a master regulator of ectoderm development essential for epidermal specification. Although previous studies have highlighted the role of p63 triggering the epidermal transcriptomic program, its precise mechanism of target gene regulation in the complex context of a developing embryo remains poorly understood. Here, we used zebrafish embryos to analyze in vivo how p63 regulates the expression of its target genes during development. We generated tp63-knock-out mutants that recapitulate human phenotypes and show down-regulated epidermal gene expression. Following p63-binding dynamics during development, we found two distinct functions clearly separated in space and time. During early development, p63 binds enhancers associated to neural genes, where it limits Sox3 binding and reduces the expression of these neural genes. Indeed, we show that p63 and Sox3 are co-expressed in the neural plate border. Later in development, p63 binds enhancers associated to epidermal genes and promotes their expression, acting as a pioneer factor, as it binds to non-accessible chromatin and is required for its opening. Therefore, our results suggest that p63 is an important regulator of cell fate decisions during ectoderm specification, promoting the epidermal fate and inhibiting the neural program.
2019-06-06 | GSE123057 | GEO
Project description:The transcription factor p63 is a master regulator of ectoderm development essential for epidermal specification. Although previous studies have highlighted the role of p63 triggering the epidermal transcriptomic program, its precise mechanism of target gene regulation in the complex context of a developing embryo remains poorly understood. Here, we used zebrafish embryos to analyze in vivo how p63 regulates the expression of its target genes during development. We generated tp63-knock-out mutants that recapitulate human phenotypes and show down-regulated epidermal gene expression. Following p63-binding dynamics during development, we found two distinct functions clearly separated in space and time. During early development, p63 binds enhancers associated to neural genes, where it limits Sox3 binding and reduces the expression of these neural genes. Indeed, we show that p63 and Sox3 are co-expressed in the neural plate border. Later in development, p63 binds enhancers associated to epidermal genes and promotes their expression, acting as a pioneer factor, as it binds to non-accessible chromatin and is required for its opening. Therefore, our results suggest that p63 is an important regulator of cell fate decisions during ectoderm specification, promoting the epidermal fate and inhibiting the neural program.
2019-06-06 | GSE123056 | GEO