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ChIP-seq analysis comparing WT, TAp63-/-, and ΔNp63-/- primary murine keratinocytes

ABSTRACT: The p53 family member TP63 encodes two sets of isoforms, TAp63 and ∆Np63 isoforms, which are characterized by different N-termini and have diverse biological functions in epidermal morphogenesis and in cancer. In the skin, where their activities are best characterized, TAp63 prevents premature aging by regulating cellular senescence and genomic stability of stem cells, while ∆Np63 controls terminal differentiation of the basal cells in the epidermis. This functional diversity is surprising given that these isoforms share a high degree of similarity, including an identical DNA binding domain. To understand the mechanisms involved in the transcriptional programs leading to these diverse biological functions, we performed genome-wide analyses using p63-ChIP-seq and RNA-seq of TAp63-/- and ∆Np63-/- compared to wild-type primary mouse epidermal cells. Our data indicate that TAp63 and ∆Np63 recognize significantly different response elements on DNA and can physically and functionally interact with distinct transcription factors for the downstream regulation of their target genes. Our findings unveil previously uncharacterized transcriptomes activated by the p63 isoforms to regulate diverse biological functions in epidermal morphogenesis and homeostasis and cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE147723 | GEO | 2023/12/06

REPOSITORIES: GEO

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Gene expression profiles induced by knockdown and overexpression of p63 variants in MCF-10A mammary epithelial cell line

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2010-03-23 | E-GEOD-20286 | biostudies-arrayexpress

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2023-09-29 | GSE234979 | GEO

Late cornified envelope 1C (LCE1C) gene is a transcriptional target of TAp63.

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DeltaNp63 silencing, DNA methylation shifts and epithelial mesenchymal transition resulted from TAp63 genome editing in squamous cell carcinoma [microarray]

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2023-09-29 | GSE234978 | GEO

p63 ChIP-seq analysis comparing WT, TAp63-null, and DNp63-null primary murine keratinocytes

Project description:We performed a ChIP-seq analysis characterizing the p63 binding sites in primary keratinocytes obtained from E18.5 mice of 3 different genotypes (WT, TAp63-/-, and ΔNp63-/-). We aimed to identify the specific genomic regions bound by TAp63 and ΔNp63 in physiological conditions.

2018-03-20 | GSE79448 | GEO

Gene expression profiles induced by knockdown and overexpression of p63 variants in MCF-10A mammary epithelial cell line

2010-03-12 | GSE20286 | GEO

Transcription profiling of human cell lines from Hay Wells Syndrome-Derived TAp63alphaQ540L mutant rveals impaired transcriptional and cell growth regulatory activity

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2008-06-16 | E-GEOD-8646 | biostudies-arrayexpress

Analysis of human TAp63 regulated genes in CD4+ T cells

Project description:By comparing the comprehensive gene expression profiles between human Th17 cells overexpressing TAp63 and those with TAp63 knockdown, FOXP3 was identified as one of the downregulated genes by TAp63

2023-04-10 | GSE181427 | GEO

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2020-07-07 | PXD014261 | Pride

FANCD2 Activates Transcription of TAp63 and Suppresses Tumorigenesis

Project description:Fanconi Anemia (FA) is a rare genetic disorder characterized by an increased susceptibility to squamous cell cancers. Fifteen FA genes are known, and the encoded proteins cooperate in a common DNA repair pathway. A critical step is the monoubiquitination of the FANCD2 protein, and cells from most FA patients are deficient in this step. How monoubiquitinated FANCD2 suppresses squamous cell cancers is unknown. Here we show that Fancd2-deficient mice are prone to Ras oncogene-driven skin carcinogenesis, while Usp1-deficient mice, expressing elevated cellular levels of Fancd2-Ub, are resistant to skin tumors. Moreover, Fancd2-Ub activates the transcription of the tumor suppressor TAp63, thereby promoting cellular senescence and blocking skin tumorigenesis. For FA patients, the reduction of FANCD2-Ub and TAp63 protein levels may account for their susceptibility to squamous cell neoplasia. Taken together, Usp1 inhibition may be a useful strategy for upregulating TAp63 and preventing or treating squamous cell cancers in the general non-FA population. Examination of FANCD2 binding after UV treatment in 293T cells

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