HNF1 regulates critical functions of the human epididymis epithelium. [ChIP-Seq]

HNF1α and HNF1β recognize the same DNA consensus sequence in the genome, to which they bind as homodimers or heterodimers. Both factors share a high degree of homology their DNA binding and dimerization (N-terminus) regions but have a more divergent C-terminal transactivation domain. HNF1β is essential for the generation of a functional male reproductive tract in mice and genital tract abnormalities are evident in humans with recessive mutations in HNF1β. The functions of HNF1α and HNF1β have been studied in epithelia from other several tissues (liver, kidney, intestine, and pancreas) but their role in the adult human epididymis epithelium (HEE) remains unexplored. We established that HNF1α/β are expressed in caput HEE cells and are predicted to occupy cis-regulatory elements in these cells. We next used Chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) to examine the genome-wide binding of HNF1 in caput HEE cells from two donors. The majority of the HNF1 peaks localized within intergenic regions and intronic regions rather than at promoter regions. This implies an important role for HNF1 in regulating gene expression though distal cis-regulatory elements. HNF1 occupies many genomic sites that are close to genes with a role in epididymis epithelial transport. Examination of HNF1 binding in Caput HEE cells. There are two replicates of the HNF1 ChIP-seq plus input samples (control).