Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Contextual epigenetic regulation of lung adenocarcinoma by GATA6 [ATAC-Seq]

ABSTRACT: Lineage selective transcription factors (TFs) are important regulators of tumorigenesis, but their biological functions are often context dependent and their epigenetic mechanisms of action undefined. In this study, we uncover a conditional role for the endodermal and pulmonary specifying TF GATA6 during the initiation and progression of Kras mutant lung adenocarcinoma (LUAD). Inhibition of Gata6 in genetically engineered mouse models dampens the proliferation and increases the differentiation of LUAD tumors. These effects are influenced in part by the epithelial cell type that is targeted for transformation. In lung cancer cells derived from surfactant protein C expressing progenitors, we identify multiple genomic loci that are bound by GATA6. Moreover, suppression of Gata6 in these cells significantly alters chromatin accessibility, particularly at distal enhancer elements. Analogous to its paradoxical activity in the developing lungs, GATA6 expression fluctuates during different stages of LUAD progression and can control diverse lineage gene expression networks associated with cell proliferation, alveolar specification, BMP signaling, and epithelial plasticity. These findings demonstrate how GATA6 can broadly modulate the epigenome of lung tumor cells, which in turn may potentiate its divergent functions during cancer progression

ORGANISM(S): Mus musculus

PROVIDER: GSE124602 | GEO | 2020/03/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Contextual epigenetic regulation of lung adenocarcinoma by GATA6 [RNA-Seq]

Project description:Lineage selective transcription factors (TFs) are important regulators of tumorigenesis, but their biological functions are often context dependent and their epigenetic mechanisms of action undefined. In this study, we uncover a conditional role for the endodermal and pulmonary specifying TF GATA6 during the initiation and progression of Kras mutant lung adenocarcinoma (LUAD). Inhibition of Gata6 in genetically engineered mouse models dampens the proliferation and increases the differentiation of LUAD tumors. These effects are influenced in part by the epithelial cell type that is targeted for transformation. In lung cancer cells derived from surfactant protein C expressing progenitors, we identify multiple genomic loci that are bound by GATA6. Moreover, suppression of Gata6 in these cells significantly alters chromatin accessibility, particularly at distal enhancer elements. Analogous to its paradoxical activity in the developing lungs, GATA6 expression fluctuates during different stages of LUAD progression and can control diverse lineage gene expression networks associated with cell proliferation, alveolar specification, BMP signaling, and epithelial plasticity. These findings demonstrate how GATA6 can broadly modulate the epigenome of lung tumor cells, which in turn may potentiate its divergent functions during cancer progression

2020-03-05 | GSE124603 | GEO

Contextual epigenetic regulation of lung adenocarcinoma by GATA6 [ChIP-Seq]

2020-03-05 | GSE124601 | GEO

Lung adenocarcinoma metastasis is suppressed by the alveolar lineage transcription factors GATA6 and HOPX.

Project description:Molecular programs that mediate normal cell differentiation are required for oncogenesis and tumor cell survival in certain types of cancers. How cell lineage restricted genes specifically influence metastatic progression is poorly defined. In lung cancers, we uncovered an alveolar cell-selective transcriptional program that preferentially correlates with lung adenocarcinoma metastasis. This program is required for epithelial specification in the distal airways and is partially regulated by the lineage transcription factors GATA6 and HOPX. These factors cooperatively restrain the metastatic competence of adenocarcinoma cells, without affecting their survival, through the modulation of alveologenic and invasogenic target genes. Thus, GATA6 and HOPX are critical nodes in a lineage-selective pathway that directly links alveolar cell fate with metastasis suppresion in the lung adenocarcinoma subtype. mRNA profiles of human lung Adenocarcinoma PC9 cell lines infected with lentivirus harboring shRNA of control (Arab1) and shRNA of both GATA6 and HOPX were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.

2013-06-10 | E-GEOD-39121 | biostudies-arrayexpress

Contextual epigenetic regulation of lung adenocarcinoma by GATA6

Project description:Contextual epigenetic regulation of lung adenocarcinoma by GATA6

| PRJNA512628 | ENA

Lung adenocarcinoma metastasis is suppressed by the alveolar lineage transcription factors GATA6 and HOPX.

Project description:Molecular programs that mediate normal cell differentiation are required for oncogenesis and tumor cell survival in certain cancers. How cell-lineage-restricted genes specifically influence metastasis is poorly defined. In lung cancers, we uncovered a transcriptional program that is preferentially associated with distal airway epithelial differentiation and lung adenocarcinoma (ADC) progression. This program is regulated in part by the lineage transcription factors GATA6 and HOPX. These factors can cooperatively limit the metastatic competence of ADC cells, by modulating overlapping alveolar differentiation and invasogenic target genes. Thus, GATA6 and HOPX are critical nodes in a lineage-selective pathway that directly links effectors of airway epithelial specification to the inhibition of metastasis in the lung ADC subtype.

2013-06-10 | GSE39121 | GEO

The Effect of GATA6 on miRNA in Lung Development

Project description:Gata6 regulates lung epithelial stem cell development and airway regeneration. Here, the expression profile of microRNA was investigated when Gata6 was depleted during lung development.

2011-03-01 | GSE25874 | GEO

Genes regulated by GATA6 in the lung

Project description:Epithelial organs including the lung are known to possess regenerative abilities through activation of endogenous stem cell populations but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation in Gata6 null lung epithelium. This expansion of BASCs is the result of a dramatic increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the non-canonical Wnt receptor Fzd2 is down-regulated in Gata6 mutants and increased Fzd2 or decreased β-catenin expression rescues, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, we show that canonical Wnt signaling is activated in the niche containing BASCs and forced activation of Wnt signaling leads to a dramatic increase in BASC numbers. Moreover, Gata6 is required for proper lung epithelial regeneration and postnatal loss of Gata6 leads to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6 regulated Wnt signaling controls the balance between stem/progenitor expansion and epithelial differentiation required for both lung development and regeneration. Keywords: gene targets in knockout mouse model

2008-04-15 | GSE11165 | GEO

Transcription profiling ofmouse wild type and GATA6 null lung

Project description:Epithelial organs including the lung are known to possess regenerative abilities through activation of endogenous stem cell populations but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation in Gata6 null lung epithelium. This expansion of BASCs is the result of a dramatic increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the non-canonical Wnt receptor Fzd2 is down-regulated in Gata6 mutants and increased Fzd2 or decreased Î²-catenin expression rescues, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, we show that canonical Wnt signaling is activated in the niche containing BASCs and forced activation of Wnt signaling leads to a dramatic increase in BASC numbers. Moreover, Gata6 is required for proper lung epithelial regeneration and postnatal loss of Gata6 leads to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6 regulated Wnt signaling controls the balance between stem/progenitor expansion and epithelial differentiation required for both lung development and regeneration. Experiment Overall Design: 3 replicates of each condition-wild-type and GATA6 null tissue. 6 total samples.

2008-06-11 | E-GEOD-11165 | biostudies-arrayexpress

Contextual epigenetic regulation of lung adenocarcinoma by GATA6 [RNA-Seq]

Project description:Contextual epigenetic regulation of lung adenocarcinoma by GATA6 [RNA-Seq]

| PRJNA512631 | ENA

Contextual epigenetic regulation of lung adenocarcinoma by GATA6 [ChIP-Seq]

Project description:Contextual epigenetic regulation of lung adenocarcinoma by GATA6 [ChIP-Seq]

| PRJNA512630 | ENA