Analysis of gene regulation by the TP63 isoforms deltaNp63alpha and deltaNp63beta using ChIPseq of p63 and H3K27ac
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE283359 | GEO | 2024/12/13
REPOSITORIES: GEO
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Project description:We analyzed the transcriptome changes of the colon carcinoma cell line HCT116 TP53-/- in response to expression of the TP63 isoforms deltaNp63alpha or deltaNp63beta. The goal was to understand how these C-terminal isoforms of p63 might differentially regulate gene expression.
2024-12-13 | GSE283357 | GEO
Project description:We analyzed the transcriptome changes of the basal mammary epithelial human cell line MCF10A in response to expression of the TP63 isoforms deltaNp63alpha or deltaNp63beta. The goal was to understand how these C-terminal isoforms of p63 might differentially regulate gene expression.
2025-07-30 | GSE296914 | GEO
Project description:Analysis of gene regulation by the TP63 isoforms deltaNp63alpha and deltaNp63beta using ChIPseq of p63 and H3K27ac
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Project description:Analysis of gene regulation by the TP63 isoforms deltaNp63alpha and deltaNp63beta
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Project description:Analysis of gene regulation by the TP63 isoforms deltaNp63alpha and deltaNp63beta in MCF10A cells
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Project description:The p53 homologue, p63, is critical for normal epidermal development. While overexpression of deltaNp63alpha has been reported in squamous cell cancers, the contribution of p63 to cancer pathogenesis remains unclear. We previously demonstrated that overexpressed deltaNp63alpha aberrantly maintains proliferation of primary epidermal keratinocytes under conditions that normally induce growth arrest and differentiation. To identify target genes impacted by dysregulated deltaNp63alpha that may contribute to squamous cancer development and progression, microarray analyses were performed. Herein we report that elevated deltaNp63alpha differentially regulates genes in primary mouse keratinocytes involved in a variety of cellular functions, including cell cycle regulation, differentiation, skin barrier formation and function, apoptosis, host defense/inflammation, adhesion, migration and invasion. Of note, multiple protease inhibitor mRNAs were coordinately downregulated under both proliferating and differentiating culture conditions. These downregulated genes include two serine protease inhibitors: maspin (serpinB5) and plasminogen activator inhibitor-2 (PAI-2; serpinB2), as well as a tissue inhibitor of metalloproteinase-3 (TIMP-3). Correspondingly, secreted levels of TIMP-3 and PAI-2 protein declined in the presence of dysregulated deltaNp63alpha, while secreted maspin protein levels remained stable. Intracellular maspin protein expression decreased in response to overexpressed deltaNp63alpha, as did intracellular PAI-2. Unlike PAI-2 and maspin, TIMP-3 protein was not detected intracellularly in control or deltaNp63alpha-overexpressing keratinocytes, supporting a solely extracellular function for TIMP-3. Electrophoretic mobility shift assays using a p53/p63 consensus DNA binding sequence from the maspin promoter revealed binding of an endogenous transcription factor(s) to the consensus sequence in normal keratinocytes that was disrupted by overexpressed deltaNp63alpha. This binding was also interrupted by the addition of a p73 antibody, but not antibodies to p63 or p53, and was absent in samples derived from p73(-/-) keratinocytes, confirming p73 as a constituent of the endogenous transcription factor complex. These data suggest protease inhibitors as novel targets of dysregulated deltaNp63alpha in cancer pathogenesis.
2013-02-26 | GSE34862 | GEO
Project description:The p53 homologue, p63, is critical for normal epidermal development. While overexpression of deltaNp63alpha has been reported in squamous cell cancers, the contribution of p63 to cancer pathogenesis remains unclear. We previously demonstrated that overexpressed deltaNp63alpha aberrantly maintains proliferation of primary epidermal keratinocytes under conditions that normally induce growth arrest and differentiation. To identify target genes impacted by dysregulated deltaNp63alpha that may contribute to squamous cancer development and progression, microarray analyses were performed. Herein we report that elevated deltaNp63alpha differentially regulates genes in primary mouse keratinocytes involved in a variety of cellular functions, including cell cycle regulation, differentiation, skin barrier formation and function, apoptosis, host defense/inflammation, adhesion, migration and invasion. Of note, multiple protease inhibitor mRNAs were coordinately downregulated under both proliferating and differentiating culture conditions. These downregulated genes include two serine protease inhibitors: maspin (serpinB5) and plasminogen activator inhibitor-2 (PAI-2; serpinB2), as well as a tissue inhibitor of metalloproteinase-3 (TIMP-3). Correspondingly, secreted levels of TIMP-3 and PAI-2 protein declined in the presence of dysregulated deltaNp63alpha, while secreted maspin protein levels remained stable. Intracellular maspin protein expression decreased in response to overexpressed deltaNp63alpha, as did intracellular PAI-2. Unlike PAI-2 and maspin, TIMP-3 protein was not detected intracellularly in control or deltaNp63alpha-overexpressing keratinocytes, supporting a solely extracellular function for TIMP-3. Electrophoretic mobility shift assays using a p53/p63 consensus DNA binding sequence from the maspin promoter revealed binding of an endogenous transcription factor(s) to the consensus sequence in normal keratinocytes that was disrupted by overexpressed deltaNp63alpha. This binding was also interrupted by the addition of a p73 antibody, but not antibodies to p63 or p53, and was absent in samples derived from p73(-/-) keratinocytes, confirming p73 as a constituent of the endogenous transcription factor complex. These data suggest protease inhibitors as novel targets of dysregulated deltaNp63alpha in cancer pathogenesis. Keratinocytes were transduced with adenoviruses encoding deltaNp63alpha. Keratinocytes were either maintained in low calcium conditions (0.05 mM for 24 hours) (n=6) or high calcium conditions (0.12 mM for 24 hours) (n=6). Control samples consisted of keratinocytes transduced with adenoviruses encoding beta-galactosidase also treated with low calcium (n=6) and high calcium (n=6) conditions. Twelve technical repeat microarray experiments were conducted, pairing high-calcium deltaNp63alpha samples with high-calcium beta-galactosidase samples (n=6) and low-calcium deltaNp63alpha samples with low-calcium beta-galactosidase samples (n=6). Six of the technical repeats were conducted as reverse-fluoro experiments.
2013-02-26 | E-GEOD-34862 | biostudies-arrayexpress
Project description:p63, a homologue of the tumor suppressor p53, is critical for the development and maintenance of squamous epithelia. p63 is specifically expressed in the basal layers of stratified epithelial tissues and is considered a specific marker for cells of this type. The role of p63 in tumorigenesis remains poorly defined. Numerous studies have highlighted the oncogenic potential of the predominant p63 isoform DeltaNp63alpha; however, data suggest that other p63 proteins can act as tumor suppressors or alter the metastatic potential of tumors. DeltaNp63alpha can act as a transcriptional repressor, but the link between the transcriptional functions of p63 and its biological role is still unclear. In this study, we used a loss-of-function approach to investigate the transcriptional programs controlled by p63. Disruption of p63 in squamous cell lines resulted in down-regulation of transcripts specifically expressed in squamous tissues and a significant alteration of keratinocyte differentiation. Interestingly, we found that disruption of p63 led to up-regulation of markers of nonepithelial tissues (mesenchyme and neural tissue) in both primary and immortalized squamous cells. Many of these up-regulated genes are associated with increased capacity for invasion and metastasis in tumors. Furthermore, loss of p63 expression was accompanied by a shift toward mesenchymal morphology and an increase in motility in primary keratinocytes and squamous cell lines. We conclude that loss of endogenous p63 expression results in up-regulation of genes associated with invasion and metastasis, and predisposes to a loss of epithelial and acquisition of mesenchymal characteristics. These findings have implications for the role of p63 in both development and tumorigenesis.
2007-11-11 | E-GEOD-4975 | biostudies-arrayexpress
Project description:The placenta plays a crucial role in pregnancy success. deltaNp63alpha (p63), a transcription factor from the TP53 family, is highly expressed in villous cytotrophoblasts (CTBs), the epithelial stem cells of the human placenta, and has been shown to be involved in CTB maintenance and differentiation. In this study, we set out to identify mechanism(s) of action of p63, by identifying its downstream targets. We evaluate gene expression changes following overexpression and knockdown of p63 in the JEG3 choriocarcinoma cell line, using microarray-based RNA profiling. We identify High temperature requirement A4 (HTRA4), a placenta-specific serine protease involved in trophoblast differentiation and altered in preeclampsia, as a gene reciprocally regulated by p63, and characterize its expression in primary human placental tissues by RNAseq (PMID 34540826; GSE173372) and in situ hybridization. Forced overexpression of deltaNp63alpha in JEG-3 was obtained by pCMV lentiviral vector infection (empty vector used as control). ) The pLKO.1-based non-targeting scramble and p63-specific short hairpin (shRNA) lentiviral plasmids were used for gene knock-down. Vectors were previously described in Li et al Am J Pathol. 2014 PMID: 25307348.
2024-03-27 | GSE251742 | GEO
Project description:This study was designed to examine the requirement for the p63 transcription factor in Squamous Cell Carcinoma (SCC) tumor maintenance in an in vivo murine system. A tamoxifen-inducible Keratin 14-driven Cre recombinase transgene was used to conditionally excise p63 in advanced murine SCC tumors. These data show the context-dependent regulation of p63 target genes in cancer. Total RNA from murine Squamous Cell Carcinoma tumors was examined 1-3 days following genomic excision of TP63 in Keratin 14-expressing tumor cells.
2013-08-06 | E-GEOD-45929 | biostudies-arrayexpress