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ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE141607 | GEO | 2020/05/09

REPOSITORIES: GEO

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ZBED2 is an antagonist of interferon regulatory factor 1 and modifies cell identity in pancreatic cancer.

Project description:Lineage plasticity is a prominent feature of pancreatic ductal adenocarcinoma (PDA) cells, which can occur via deregulation of lineage-specifying transcription factors. Here, we show that the zinc finger protein ZBED2 is aberrantly expressed in PDA and alters tumor cell identity in this disease. Unexpectedly, our epigenomic experiments reveal that ZBED2 is a sequence-specific transcriptional repressor of IFN-stimulated genes, which occurs through antagonism of IFN regulatory factor 1 (IRF1)-mediated transcriptional activation at cooccupied promoter elements. Consequently, ZBED2 attenuates the transcriptional output and growth arrest phenotypes downstream of IFN signaling in multiple PDA cell line models. We also found that ZBED2 is preferentially expressed in the squamous molecular subtype of human PDA, in association with inferior patient survival outcomes. Consistent with this observation, we show that ZBED2 can repress the pancreatic progenitor transcriptional program, enhance motility, and promote invasion in PDA cells. Collectively, our findings suggest that high ZBED2 expression is acquired during PDA progression to suppress the IFN response pathway and to promote lineage plasticity in this disease.

| S-EPMC7261015 | biostudies-literature

ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer (ChIP-seq)

Project description:Lineage plasticity is a prominent feature of pancreatic ductal adenocarcinoma (PDA) cells, which can occur via deregulation of lineage-specifying transcription factors. Here, we show that the zinc finger protein ZBED2 is aberrantly expressed in PDA and regulates tumor cell identity in this disease. Unexpectedly, our epigenomic experiments reveal that ZBED2 is a sequence-specific transcriptional repressor of interferon-stimulated genes, which occurs through antagonism of Interferon Regulatory Factor 1 (IRF1)-mediated transcriptional activation at co-occupied promoter elements. Consequently, ZBED2 attenuates the transcriptional output and growth arrest phenotypes downstream of interferon signaling in multiple PDA cell line models. We also found that ZBED2 is preferentially expressed in the squamous molecular subtype of human PDA, in association with inferior patient survival outcomes. Consistent with this observation, we show that ZBED2 can repress the pancreatic progenitor transcriptional program, enhance motility, and promote invasion in PDA cells. Collectively, our findings suggest that high ZBED2 expression is acquired during PDA progression to suppress the interferon response pathway and to promote lineage plasticity in this disease.

2020-05-09 | GSE141606 | GEO

ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer (RNA-seq)

Project description:Lineage plasticity is a prominent feature of pancreatic ductal adenocarcinoma (PDA) cells, which can occur via deregulation of lineage-specifying transcription factors. Here, we show that the zinc finger protein ZBED2 is aberrantly expressed in PDA and regulates tumor cell identity in this disease. Unexpectedly, our epigenomic experiments reveal that ZBED2 is a sequence-specific transcriptional repressor of interferon-stimulated genes, which occurs through antagonism of Interferon Regulatory Factor 1 (IRF1)-mediated transcriptional activation at co-occupied promoter elements. Consequently, ZBED2 attenuates the transcriptional output and growth arrest phenotypes downstream of interferon signaling in multiple PDA cell line models. We also found that ZBED2 is preferentially expressed in the squamous molecular subtype of human PDA, in association with inferior patient survival outcomes. Consistent with this observation, we show that ZBED2 can repress the pancreatic progenitor transcriptional program, enhance motility, and promote invasion in PDA cells. Collectively, our findings suggest that high ZBED2 expression is acquired during PDA progression to suppress the interferon response pathway and to promote lineage plasticity in this disease.

2020-05-09 | GSE141605 | GEO

ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer

Project description:ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer

| PRJNA594031 | ENA

ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer (ChIP-seq)

Project description:ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer (ChIP-seq)

| PRJNA594034 | ENA

ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer (RNA-seq)

Project description:ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer (RNA-seq)

| PRJNA594035 | ENA

Interferon regulatory factor 1 (IRF1) controls the metabolic programmes of low-grade pancreatic cancer cells

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

2022-05-09 | GSE165950 | GEO

Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis

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Interferon Regulatory Factor 6 Determines Epithelial Cell Development and Immunity

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2023-11-01 | GSE245972 | GEO

Atrial Identity Is Determined by A COUP-TFII Regulatory Network

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

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