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This process requires distinct specialized functions in the head, body, and tail of the duct. These region\u2010specific properties are maintained by distinct gene expression profiles which are governed by transcription factor networks, non\u2010coding RNA<\/jats:styled-content>s, and other factors.<\/jats:p><\/jats:sec>Materials and methods<\/jats:title>We used genome\u2010wide protocols including DN<\/jats:styled-content>ase\u2010seq, RNA<\/jats:styled-content>\u2010seq and ChIP<\/jats:styled-content>\u2010seq to characterize open (active) chromatin, the transcriptome and occupancy of specific transcription factors (TF<\/jats:styled-content>s) respectively, in caput, corpus, and cauda segments of adult human epididymis tissue and primary human epididymis epithelial (HEE<\/jats:styled-content>) cell cultures derived from them. RNA<\/jats:styled-content>\u2010seq following TF<\/jats:styled-content> depletion or activation, combined with gene ontology analysis also determined TF<\/jats:styled-content> targets.<\/jats:p><\/jats:sec>Results<\/jats:title>Among regional differentially expressed transcripts were epithelial\u2010selective transcription factors (TF<\/jats:styled-content>s), microRNA<\/jats:styled-content>s, and antiviral response genes. Caput\u2010enriched TF<\/jats:styled-content>s included hepatocyte nuclear factor 1 (HNF<\/jats:styled-content>1) and the androgen receptor (AR<\/jats:styled-content>), both of which were also predicted to occupy cis\u2010regulatory elements identified as open chromatin in HEE<\/jats:styled-content> cells. HNF<\/jats:styled-content>1 targets were identified genome\u2010wide using ChIP<\/jats:styled-content>\u2010seq, in HEE<\/jats:styled-content> cells. Next, siRNA<\/jats:styled-content>\u2010mediated depletion of HNF<\/jats:styled-content>1 revealed a pivotal role for this TF<\/jats:styled-content> in coordinating epithelial water and solute transport in caput epithelium. The importance of AR<\/jats:styled-content> in HEE<\/jats:styled-content> cells was shown by AR<\/jats:styled-content> ChIP<\/jats:styled-content>\u2010seq, and by RNA<\/jats:styled-content>\u2010seq after synthetic androgen (R1881) treatment. AR<\/jats:styled-content> has a distinct transcriptional program in the HEE<\/jats:styled-content> cells and likely recruits different co\u2010factors (RUNX<\/jats:styled-content>1 and CEBP<\/jats:styled-content>\u03b2) in comparison to those used in prostate epithelium.<\/jats:p><\/jats:sec>Discussion and Conclusion<\/jats:title>Our data identify many transcription factors that regulate the development and differentiation of HEE<\/jats:styled-content> cells. Moreover, a comparison between immature and adult HEE<\/jats:styled-content> cells showed key TF<\/jats:styled-content>s in the transition to fully differentiated function of this epithelium. These data may help identify new targets to treat male infertility and have the potential to open new avenues for male contraception.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12629","type":"journal-article","created":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T04:07:10Z","timestamp":1556856430000},"page":"741-747","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Transcriptional networks in the human epididymis"],"prefix":"10.1111","volume":"7","author":[{"given":"J. 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