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KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [RNA-Seq]

ABSTRACT: KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [RNA-Seq]

PROVIDER: PRJNA433840 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6707280.fastq.gz	Fastqsanger.gz
	SRR6707281.fastq.gz	Fastqsanger.gz
	SRR6707282.fastq.gz	Fastqsanger.gz
	SRR6707283.fastq.gz	Fastqsanger.gz
	SRR6707284.fastq.gz	Fastqsanger.gz

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KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis

Project description:KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis

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KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [RNA-Seq]

Project description:KMT2D plays a critical role in the control of epithelial enhancers and p63 target gene expression, including the re-quirement of KMT2D for the maintenance of epithelial progenitor gene expression and the coordination of proper terminal differentiation.

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KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis [ChIP-Seq]

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KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis.

Project description:Epithelial tissues rely on a highly coordinated balance between self-renewal, proliferation, and differentiation, disruption of which may drive carcinogenesis. The epigenetic regulator KMT2D (MLL4) is one of the most frequently mutated genes in all cancers, particularly epithelial cancers, yet its normal function in these tissues is unknown. Here, we identify a novel role for KMT2D in coordinating this fine balance, as depletion of KMT2D from undifferentiated epidermal keratinocytes results in reduced proliferation, premature spurious activation of terminal differentiation genes, and disorganized epidermal stratification. Genome-wide, KMT2D interacts with p63 and is enriched at its target enhancers. Depletion of KMT2D results in a broad loss of enhancer histone modifications H3 Lys 4 (H3K4) monomethylation (H3K4me1) and H3K27 acetylation (H3K27ac) as well as reduced expression of p63 target genes, including key genes involved in epithelial development and adhesion. Together, these results reveal a critical role for KMT2D in the control of epithelial enhancers and p63 target gene expression, including the requirement of KMT2D for the maintenance of epithelial progenitor gene expression and the coordination of proper terminal differentiation.

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KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-02-12 | GSE110475 | GEO

Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dynamic enhancers (RNA-Seq)

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

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Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dynamic enhancers (ChIP-Seq)

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2015-05-01 | GSE59824 | GEO

Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dynamic enhancers (RNA-Seq)

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