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Metzger, E.* ; Wissmann, M.* ; Yin, N.* ; Müller, J.M.* ; Schneider, R.* ; Peters, A.H.* ; Günther, T.* ; Buettner, R.* ; Schule, R.*

LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription.

Nature 437, 436-439 (2005)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Gene regulation in eukaryotes requires the coordinate interaction of chromatin-modulating proteins with specific transcription factors such as the androgen receptor. Gene activation and repression is specifically regulated by histone methylation status at distinct lysine residues. Here we show that lysine-specific demethylase 1 (LSD1; also known as BHC110) co-localizes with the androgen receptor in normal human prostate and prostate tumour. LSD1 interacts with androgen receptor in vitro and in vivo, and stimulates androgen-receptor-dependent transcription. Conversely, knockdown of LSD1 protein levels abrogates androgen-induced transcriptional activation and cell proliferation. Chromatin immunoprecipitation analyses demonstrate that androgen receptor and LSD1 form chromatin-associated complexes in a ligand-dependent manner. LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9 (H3-K9), thereby leading to de-repression of androgen receptor target genes. Furthermore, we identify pargyline as an inhibitor of LSD1. Pargyline blocks demethylation of H3-K9 by LSD1 and consequently androgen-receptor-dependent transcription. Thus, modulation of LSD1 activity offers a new strategy to regulate androgen receptor functions. Here, we link demethylation of a repressive histone mark with androgen-receptor-dependent gene activation, thus providing a mechanism by which demethylases control specific gene expression.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2005
HGF-Berichtsjahr 0
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Quellenangaben Band: 437, Heft: 7057, Seiten: 436-439 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Functional Epigenetics (IFE)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502800-001
PubMed ID 16079795
DOI 10.1038/nature04020
Erfassungsdatum 2005-12-31
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