Cooperative demethylation by jmjd2c and lsd1 promotes androgen receptor-dependent gene expression

ABSTRACT Posttranslational modifications of histones, such as methylation, regulate chromatin structure and gene expression1. Recently, lysine-specific demethylase 1 (LSD1)2, the first

histone demethylase, was identified. LSD1 interacts with the androgen receptor and promotes androgen-dependent transcription of target genes by ligand-induced demethylation of mono- and

dimethylated histone H3 at Lys 9 (H3K9)3 only. Here, we identify the Jumonji C (JMJC)4 domain-containing protein JMJD2C5,6 as the first histone tridemethylase regulating androgen receptor

function. JMJD2C interacts with androgen receptor _in vitro_ and _in vivo_. Assembly of ligand-bound androgen receptor and JMJD2C on androgen receptor-target genes results in demethylation

of trimethyl H3K9 and in stimulation of androgen receptor-dependent transcription. Conversely, knockdown of JMJD2C inhibits androgen-induced removal of trimethyl H3K9, transcriptional

activation and tumour cell proliferation. Importantly, JMJD2C colocalizes with androgen receptor and LSD1 in normal prostate and in prostate carcinomas. JMJD2C and LSD1 interact and both

demethylases cooperatively stimulate androgen receptor-dependent gene transcription. In addition, androgen receptor, JMJD2C and LSD1 assemble on chromatin to remove methyl groups from mono,

di and trimethylated H3K9. Thus, our data suggest that specific gene regulation requires the assembly and coordinate action of demethylases with distinct substrate specificities. Access

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SIMILAR CONTENT BEING VIEWED BY OTHERS CHROMATIN BINDING OF FOXA1 IS PROMOTED BY LSD1-MEDIATED DEMETHYLATION IN PROSTATE CANCER Article 31 August 2020 A CARBOXY-TERMINAL UBIQUITYLATION SITE

REGULATES ANDROGEN RECEPTOR ACTIVITY Article Open access 05 January 2024 PIM1 PHOSPHORYLATION OF THE ANDROGEN RECEPTOR AND 14-3-3 Ζ REGULATES GENE TRANSCRIPTION IN PROSTATE CANCER Article

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Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank S. Gray for generously providing reagents. We thank K. Fischer, L. Walz, F. Klott and S. Vomstein for excellent

technical assistance. We are obliged to M. Hoffmann and A. Schwentek from the sequencing core facility. We thank M. Follo for help with editing the manuscript. This work was supported by

grants from the Deutsche Forschungsgemeinschaft (SFB 747/P2, Schu 688/7-1, and Schu 688/9-1), the Dr. Hans Messner-Stiftung, and the Deutsche Krebshilfe (10-2019-Bu I) to R.S. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Universitäts-Frauenklinik und Zentrum für Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, Freiburg, 79106, Germany

Melanie Wissmann, Na Yin, Judith M. Müller, Holger Greschik, Thomas Günther, Eric Metzger & Roland Schüle * Research Institute of Molecular Pathology (IMP), The Vienna Biocenter, Dr.

Bohrgasse 7, Vienna, 1030, Austria Barna D. Fodor & Thomas Jenuwein * Max-Planck-Institut für Immunbiologie, Stübeweg 51, Freiburg, 79108, Germany Christine Vogler & Robert Schneider

* Institut für Pathologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, Bonn, 53127, Germany Reinhard Buettner Authors * Melanie Wissmann View author publications You can also

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ARTICLE Wissmann, M., Yin, N., Müller, J. _et al._ Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. _Nat Cell Biol_ 9, 347–353 (2007).

https://doi.org/10.1038/ncb1546 Download citation * Received: 25 October 2006 * Accepted: 02 January 2007 * Published: 04 February 2007 * Issue Date: March 2007 * DOI:

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