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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE72147 | GEO | 2015/11/21

SECONDARY ACCESSION(S): PRJNA293197

REPOSITORIES: GEO

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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.

| S-EPMC4739765 | biostudies-literature

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

2015-11-21 | E-GEOD-72147 | biostudies-arrayexpress

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.

2015-11-22 | E-GEOD-72146 | biostudies-arrayexpress

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

2015-11-22 | E-GEOD-72145 | biostudies-arrayexpress

ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas (RNA-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. Epidermal basal stem cells from ETS2(T72D) super-activated epidermis and normal epidermis were FACS-prufied for RNA-sequencing.

2015-11-22 | E-GEOD-74868 | biostudies-arrayexpress

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

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

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

2015-11-22 | GSE74867 | GEO

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

2015-11-22 | GSE72146 | GEO

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

2015-11-22 | GSE72145 | GEO