Transcription factor that is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites (By similarity). Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; activates GLUT2 transcription. Involved in regulation of neuronal-specific transcription. Involved in regulation of spermatogenesis; required for the maintenance of the testicular germ cell population and male fertility. Interacts with FOXA2. Restricted mainly to endoderm-derived tissues (lung, liver, stomach, and small intestine), also present additionally in ovary, testis, heart, and adipose tissue, but missing from lung. Expression peaks around day 15.5 of gestation. Expressed from day 6 to day 70 during postnatal testicular development. Reduced expression levels of several HNF3 target genes (phosphoenolpyruvate carboxykinase, transferrin, tyrosine aminotransferase) by 50 to 70%,. The germinal epithelium of testes is characterized by a loss of germ cells secondary to an increase in germ cell apoptosis that ultimately leads to a Sertoli cell-only syndrome. Significantly lower blood glucose in fasted mice.