Dataset Information

Gene expression profiling of KLF5, GATA4 and GATA6 knock down in YCC3/AGS/KATOIII cell lines

ABSTRACT: Three transcription factors KLF5, GATA4 and GATA6 are recurrently amplified in multiple gastric cancer cohorts, representing one type of lineage-survival oncogenes in gastric cancer. ChIP-Seq analysis of these three factors in multiple cell lines revealed that significant number of genomic sites are co-occupied by KLF5 and GATA4 and/or GATA6. Integrative analysis of ChIP-Seq and gene expression identified several targets of the three transcription factors in both cell lines and primary tumors, including HNF4A. These results suggest that KLF5, GATA4 and GATA6 interact and co-operate to regulate HNF4A and other genes to promote tumorigenesis in gastric cancer. Gene expression profiling of KLF5, GATA4 and GATA6 knock down in YCC3/AGS/KATOIII cells

OTHER RELATED OMICS DATASETS IN: PRJNA224584PRJNA150983PRJNA224585PRJNA122965PRJNA144797PRJNA152559PRJNA224586

ORGANISM(S): Homo sapiens

DISEASE(S): Gastric Cancer

SUBMITTER: Na-Yu Chia Patrick Tan Niantao Deng

PROVIDER: E-GEOD-51704 | ArrayExpress | 2014-09-05

SECONDARY ACCESSION(S): GSE51704PRJNA224586

REPOSITORIES: GEO, ArrayExpress

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 4 of 4

Publications

Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric cancer development.

Chia Na-Yu NY Deng Niantao N Das Kakoli K Huang Dachuan D Hu Longyu L Zhu Yansong Y Lim Kiat Hon KH Lee Ming-Hui MH Wu Jeanie J Sam Xin Xiu XX Tan Gek San GS Wan Wei Keat WK Yu Willie W Gan Anna A Tan Angie Lay Keng AL Tay Su-Ting ST Soo Khee Chee KC Wong Wai Keong WK Dominguez Lourdes Trinidad M LT Ng Huck-Hui HH Rozen Steve S Goh Liang-Kee LK Teh Bin-Tean BT Tan Patrick P

Gut 20140722 5

<h4>Objective</h4>Gastric cancer (GC) is a deadly malignancy for which new therapeutic strategies are needed. Three transcription factors, KLF5, GATA4 and GATA6, have been previously reported to exhibit genomic amplification in GC. We sought to validate these findings, investigate how these factors function to promote GC, and identify potential treatment strategies for GCs harbouring these amplifications.<h4>Design</h4>KLF5, GATA4 and GATA6 copy number and gene expression was examined in multipl ...[more]

PMID: 25053715

Similar Datasets

Project description:Lineage-restricted transcription factors (TFs) are frequently mutated or overexpressed in cancer and contribute toward malignant behaviors; however, the molecular bases of their oncogenic properties are largely unknown. As TF activities are difficult to inhibit directly with small molecules, the genes and pathways they regulate might represent more tractable targets for drug therapy. We studied GATA6, a TF gene that is frequently amplified or overexpressed in gastric, esophageal and pancreatic adenocarcinomas. GATA6-overexpressing gastric cancer cell lines cluster in gene expression space, separate from non-overexpressing lines. This expression clustering signifies a shared pathogenic group of genes that GATA6 may regulate through direct cis-element binding. We used chromatin immunoprecipitation and sequencing (ChIP-seq) to identify GATA6-bound genes and considered TF occupancy in relation to genes that respond to GATA6 depletion in cell lines and track with GATA6 mRNA (synexpression groups) in primary gastric cancers. Among other cellular functions, GATA6-occupied genes control apoptosis and govern the M-phase of the cell cycle. Depletion of GATA6 reduced the levels of the latter transcripts and arrested cells in G2 and M phases of the cell cycle. Synexpression in human tumor samples identified likely direct transcriptional targets substantially better than consideration only of transcripts that respond to GATA6 loss in cultured cells. Candidate target genes responded to the loss of GATA6 or its homolog GATA4 and even more to the depletion of both proteins. Many GATA6-dependent genes lacked nearby binding sites but several strongly dependent, synexpressed and GATA6-bound genes encode TFs such as MYC, HES1, RARB and CDX2. Thus, many downstream effects occur indirectly through other TFs and GATA6 activity in gastric cancer is partially redundant with GATA4. This integrative analysis of locus occupancy, gene dependency and synexpression provides a functional signature of GATA6-overexpressing gastric cancers, revealing both limits and new therapeutic directions for a challenging and frequently fatal disease.

Project description:Studies of adult mice lacking either GATA4 or GATA6 in the small intestine demonstrate roles for these factors in small intestinal biology. Deletion of Gata4 in the adult mouse intestine revealed an essential role for GATA4 in jejunal function. Deletion of Gata6 in the adult mouse ileum alters epithelial cell types and ileal enterocyte gene expression. The effect of deletion of Gata4 or Gata6 alone during embryonic small intestinal development, however, has not been examined. We recently demonstrated that loss of both factors in double conditional knockout embryos causes severe defects in jejunal development. Therefore, the goal of this study is to provide phenotypic analysis of the small intestine of single Gata4 and Gata6 conditional knockout embryos.Villin-Cre was used to delete Gata4 or Gata6 in the developing intestinal epithelium. Elimination of either GATA4 or GATA6 in the jejunum, where these factors are co-expressed, caused changes in enterocyte and enteroendocrine cell gene expression. Ectopic expression of markers of the ileal-specific bile acid metabolism pathway was induced in GATA4-deficient jejunum but not in GATA6-deficient jejunum. A subtle increase in goblet cells was also identified in jejunum of both mutants. In GATA6-deficient embryonic ileum, villus length was altered, and enterocyte gene expression was perturbed including ectopic expression of the colon marker Car1. Goblet cells were increased, and enteroendocrine cells were decreased.Overall, we show that aspects of the phenotypes observed in the small intestine of adult Gata4 and Gata6 conditional knockout mice emerge during development. The effect of eliminating GATA6 from the developing ileum was greater than that of eliminating either GATA4 or GATA6 from the developing jejunum likely reflecting functional redundancy between these factors in the jejunum. Although GATA4 and GATA6 functions overlap, our data also suggest unique functions for GATA4 and GATA6 within the developing intestine. GATA4 likely operates independently of GATA6 within the jejunum to regulate jejunal versus ileal enterocyte identity and consequently jejunal physiology. GATA6 likely regulates enteroendocrine cell differentiation cell autonomously whereas GATA4 affects this population indirectly.

			Action	DRS
	E-GEOD-51704.idf.txt	Idf
	E-GEOD-51704.processed.1.zip	Processed
	E-GEOD-51704.raw.1.zip	Raw
	E-GEOD-51704.sdrf.txt	Txt