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Series GSE66218 Query DataSets for GSE66218
Status Public on Aug 06, 2015
Title FOXA2 regulates a network of genes involved in critical functions of intestinal epithelia
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Background and Aims: The forkhead box A (FOXA) family of pioneer transcription factors is critical for the development of many endoderm-derived tissues including the lung and the liver. Here we investigate the role of FOXA2 in regulating intestinal epithelial cell function. Methods: ChIP-seq was used to identify FOXA2 binding sites genome-wide. Targets of FOXA2 were validated using ChIP-qPCR and siRNA-mediated depletion of FOXA1/2 followed by RT-qPCR. A luciferase-based assay was used to measure intracellular cAMP after FOXA1/2 modulation.Results: Peaks of FOXA2 occupancy were frequent at loci contributing to gene ontology pathways of regulation of cell migration, cell motion, and plasma membrane function. Depletion of both FOXA1 and FOXA2 led to a significant reduction in the expression of multiple transmembrane proteins including ion transporters. One of the targets was the adenosine A2B receptor, and reduced receptor mRNA levels were associated with a functional decrease in intracellular cAMP. We also observed that 30% of FOXA2 binding sites contained a GATA motif and that FOXA1/A2 depletion reduced GATA-4, but not GATA-6 protein levels. Conclusions: These data show that FOXA2 plays a critical role in regulating intestinal epithelial cell function. FOXA2 depletion affects the expression of ion transporters and other transmembrane proteins, which form a network essential for maintaining normal ion and solute transport. Moreover, we show that the FOXA and GATA families of transcription factors may work cooperatively to regulate gene expression genome-wide.
 
Overall design To determine the role of FOXA2 in regulating gene expression in intestinal epithelial cells, ChIP-seq was performed for FOXA2 in Caco2 (colorectal adenocarcinoma) cells.
 
Contributor(s) Gosalia N, Yang R, Kerschner JL, Harris A
Citation(s) 25921584
Submission date Feb 23, 2015
Last update date May 15, 2019
Contact name Ann Harris
Organization name Lurie Children's Hospital of Chicago Research Center
Street address 2430 N Halsted Street Box 211
City Chicago
State/province IL
ZIP/Postal code 60614
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (3)
GSM1617407 Caco2 Input
GSM1617408 FOXA2 ChIP-seq Replicate 1
GSM1617409 FOXA2 ChIP-seq Replicate 2
Relations
BioProject PRJNA276146
SRA SRP055446

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE66218_RAW.tar 1.1 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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