Fig. 6: Interplay between HNF4A and epigenetic machinery required for gene expression in vitro and in vivo.
From: HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements
HNF4A is required for the establishment and maintenance of the active enhancer state in vivo (top) and in vitro (bottom). HNF4A binding sites at enhancers in control livers show high H3K4me1 (dark blue) and H3K27ac (yellow) with chromatin accessibility (dark grey). HNF4A (green) interacts and recruits the MLL4 complex to enhancers and decorates enhancers with these active modifications resulting in higher gene expression (pink arrow). In cKO livers, HNF4A depletion results in loss of HNF4A mediated recruitment of MLL4 complex to enhancers (shown on right) and loss of active histone modifications resulting in reduction in gene expression. In 3T3 cells (bottom), ectopic expression of HNF4A in 3T3 cells results in morphological changes from mesenchymal to epithelial state resulting in histone modifications chromatin accessibility exhibited by cells in normal liver.
