title: DNA replication-dependent induction of gene proximity by androgen.
abstract: The male hormone androgen, working through the androgen receptor (AR), plays a major role in physiological process and disease development. Previous studies of AR mainly focus on its transcriptional activity. Here, we found that androgen-induced TMPRSS2 and ERG gene proximity is mediated by AR control of DNA replication rather than gene transcription. We demonstrate that, in both AR transactivation-positive and -negative prostate cells, androgen regulates DNA replication and androgen-induced gene proximity relies on both DNA replication-licensing and actual DNA replication activity. Androgen stimulation advances DNA replication timing of certain genomic regions, which may potentially increase gene proximity through sharing the same replication factory at a similar time. Therefore, we have revealed novel mechanisms of AR biological function, which will stimulate new research directions.
authors.affiliation: Centre for Molecular Oncology.
authors.forename: Nuria
authors.initials: N
authors.lastname: Coll-Bastus
authors.affiliation: Centre for Molecular Oncology.
authors.forename: Xueying
authors.initials: X
authors.lastname: Mao
authors.affiliation: Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK and.
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Young
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, London E1 2AT, UK.
authors.forename: Denise
authors.initials: D
authors.lastname: Sheer
authors.affiliation: Centre for Molecular Oncology, y.j.lu@qmul.ac.uk.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Lu
mesh_terms: D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D004261:DNA Replication; D013196:Dihydrotestosterone / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D011944:Receptors, Androgen / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D000071230:Transcriptional Regulator ERG
chemical_list: D000728:Androgens; C072312:ERG protein, human; D011944:Receptors, Androgen; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D013196:Dihydrotestosterone; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human