Transcription Factors GATA4 and HNF4A Control Distinct Aspects of Intestinal Homeostasis in Conjunction With the Transcription Factor CDX2

To determine whether the intestine-restricted transcription factor (TF) CDX2 functionally interacts with the endoderm-wide TF HNF4A, we crossed tissue-specific conditional Cdx2 and Hnf4a knockout mice to generate compound mutant mice. We used RNA-sequencing to profile gene expression changes in compound mutant mice compared to control mice. The compound mutant mice had a significantly worse phenotype than either single mutant, and gene expression was significantly perturbed in compound mutants compared to control mice. Total RNA isolated from control and compound mutant (Hnf4a-del;Cdx2-del) jejunal mouse intestinal epithelium was prepared for sequencing using the TruSeq RNA Sample Preparation Kit (Illumina) according to the manufacturer's instructions. 75-base-pair single-end reads were sequenced on an Illumina NextSeq 500 instrument. The data include 2 independent biological replicates per genotype.