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ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas (ChIP-Seq I)

ABSTRACT: After characterizing super-enhancer-associated chromatin dynamics accompanied by malignant progression of skin stem cells, we show that ETS family members auto-regulate themselves and a cohort of cancer-associated super-enhancer transcription factors which together are essential for tumor maintenance.

ORGANISM(S): Mus musculus

PROVIDER: GSE72145 | GEO | 2015/11/22

SECONDARY ACCESSION(S): PRJNA293199

REPOSITORIES: GEO

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ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas (ChIP-Seq II)

Project description:After characterizing super-enhancer-associated chromatin dynamics accompanied by malignant progression of skin stem cells, we show that ETS family members auto-regulate themselves and a cohort of cancer-associated super-enhancer transcription factors which together are essential for tumor maintenance. Control and ETS2(T72D) super-activated epidermal basal stem cells were FACS-purified for ChIP-sequencing.

2015-11-22 | E-GEOD-74867 | biostudies-arrayexpress

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Project description:After characterizing super-enhancer-associated chromatin dynamics accompanied by malignant progression of skin stem cells, we show that ETS family members auto-regulate themselves and a cohort of cancer-associated super-enhancer transcription factors which together are essential for tumor maintenance. Epidermal basal stem cells from ETS2(T72D) super-activated epidermis and normal epidermis were FACS-prufied for RNA-sequencing.

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ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas (ChIP-Seq I)

Project description:After characterizing super-enhancer-associated chromatin dynamics accompanied by malignant progression of skin stem cells, we show that ETS family members auto-regulate themselves and a cohort of cancer-associated super-enhancer transcription factors which together are essential for tumor maintenance. Mouse skin squamouse cell carcinoma (SCC) tumor-initiating stem cells (SCs) were FACS-purified for ChIP-sequencing.

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ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas (RNA-Seq I)

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ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas (RNA-Seq I)

Project description:After characterizing super-enhancer-associated chromatin dynamics accompanied by malignant progression of skin stem cells, we show that ETS family members auto-regulate themselves and a cohort of cancer-associated super-enhancer transcription factors which together are essential for tumor maintenance. Mouse skin squamouse cell carcinoma (SCC) tumor-initiating stem cells (SCC-SC), hair follicle stem cells (HF-SC) and epidermal stem cells (Epi-SC) were FACS-prufied for RNA-sequencing.

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The ProCisTranomic of human ETS family

Project description:ETS-domain proteins are a family of evolutionarily conserved transcription factors (TFs) critical in the development of various cancers. Despite their recognized role in oncogenesis, the proteomic landscape of ETS family members remains underexplored. This study focuses on the systematic analysis of high-throughput proteomics data to decode the protein-protein interaction (PPI) networks and signal transduction pathways regulated by ETS factors in human cellular systems. Our findings uncover key PPIs that highlight both the redundancy and specificity of ETS family proteins, with a particular emphasis on their cooperative interactions with the MYC oncogene. These shared protein networks are strongly implicated in the pathogenesis of kidney renal clear cell carcinoma (KIRC) and other cancer types. By identifying key ETS-regulated proteins, we offer insights into novel molecular mechanisms that hold potential for therapeutic targeting. This proteomics-based approach enhances our understanding of ETS family proteins' regulatory roles, laying the groundwork for future research into oncogenic pathways and their implications in clinical oncology.

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ETS family transcriptional regulators drive chromatin dynamics and malignancy in squamous cell carcinomas.

Project description:Tumor-initiating stem cells (SCs) exhibit distinct patterns of transcription factors and gene expression compared to healthy counterparts. Here, we show that dramatic shifts in large open-chromatin domain (super-enhancer) landscapes underlie these differences and reflect tumor microenvironment. By in vivo super-enhancer and transcriptional profiling, we uncover a dynamic cancer-specific epigenetic network selectively enriched for binding motifs of a transcription factor cohort expressed in squamous cell carcinoma SCs (SCC-SCs). Many of their genes, including Ets2 and Elk3, are themselves regulated by SCC-SC super-enhancers suggesting a cooperative feed-forward loop. Malignant progression requires these genes, whose knockdown severely impairs tumor growth and prohibits progression from benign papillomas to SCCs. ETS2-deficiency disrupts the SCC-SC super-enhancer landscape and downstream cancer genes while ETS2-overactivation in epidermal-SCs induces hyperproliferation and SCC super-enhancer-associated genes Fos, Junb and Klf5. Together, our findings unearth an essential regulatory network required for the SCC-SC chromatin landscape and unveil its importance in malignant progression.

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ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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