BioProject

Foxa2 is required for endoderm differentiation into the hepatic lineage. The mechanism of activation for Foxa2 during this developmental process has not been elucidated yet. More...

Foxa2 is required for endoderm differentiation into the hepatic lineage. The mechanism of activation for Foxa2 during this developmental process has not been elucidated yet. We established an in vitro system to guide ES cells differentiating into definitive endoderm (DE) cells and the following DE cells to early hepatic cells. ChIP-seq assays have been successfully performed to assess the Foxa2 binding profile. Over 50% of Foxa2 target genes in DE cells were found to be activated in hepatic cells which were at a stage later than the DE stage. Therefore, our finding at the genome-wide level proved Foxa2 serves as a pioneer factor at the DE stage. Furthermore, Foxa2 could specifically induce H3K4me2 modifications to the promoter/enhancer regions of many hepatic genes to pre-mark the chromatin, and determine the hepatic lineage differentiation competence. Our study illustrated the wide existence of Foxa2's pioneer factor function and uncovered the correlation between pioneer factor and chromatin pre-mark. These findings will be helpful for understanding the developmental process of hepatogenesis and efficiently controlling Foxa2 during hepatic induction for generating functional hepatocytes. Overall design: To further gain a genome-wide view of Foxa2's effects on its target gene expression, 3 representative time points from the ES cell differentiation process to hepatic cells were selected for cDNA microarray analysis: 1) Day 0, representing ES cells, where there was no Foxa2 expression; 2) Day 5, representing DE cells; and 3) Day 7, representing early hepatic cells. Less...