Endocrine Abstracts (2016) 42 P40 | DOI: 10.1530/endoabs.42.P40

Segment-specific enrichment of AP-2 and Runx motifs within caput- and IS-preferred androgen receptor binding sites in the mouse epididymis

Päivi Pihlajamaa1, Biseajyoti Sahu1, Olli A. Jänne2, Matti Poutanen3 & Petra Sipilä3

1Genome-Scale Biology, Research Programs Unit, University of Helsinki, Helsinki, Finland; 2Institute of Biomedicine, University of Helsinki, Helsinki, Finland; 3Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland

Epididymis is an androgen dependent organ with four main segments; initial segment (IS), caput, corpus and cauda. It is an essential site for post-testicular sperm maturation, as spermatozoa acquire fertilizing capacity during epididymal transit. Post-testicular maturation is dependent on the proteins expressed and secreted to the lumen by epididymal cells. Androgens regulate gene expression in epididymis in a segment-specific manner. Caput-specific genes are androgen regulated, whereas IS-specific genes are mainly regulated by other testicular factors. However, the basis of differential androgen responsiveness of IS and caput genes is still unknown. We have performed in vivo ChiP-seq analyses on androgen receptor (AR) in IS and caput epididymides. Our results demonstrated differential AR binding in the two segments with 20,138 and 7,072 androgen receptor-binding sites (ARBs) in caput and IS, respectively. Motif enrichment analyses for the cis-elements within the ARBs revealed that 100% of IS-preferred sites had adjacent Runx motif, whereas caput-preferred ARBs showed no enrichment for Runx motif. Instead, caput-preferred sites were enriched with contiguous AP-2α cis-elements. We then compared genome wide distribution of activating histone marks; H3K27ac and H3K4me2. Majority of genomic locations in IS and caput showed similar patterns of activating histone marks around the ARBs. However, there were still marked differences in some individual genes. In conclusion, differential enrichment for cis-elements within caput- and IS-preferred ARBs suggest that collaborating transcription factors, AP-2 and Runx, might affect the segment-specific androgen regulation of gene expression. Furthermore, differences in activating histone marks may explain some differences in gene expression profiles.

Presenting Author: Petra Sipilä, Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FINLAND. Email: petra.sipila@utu.fi

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