Histone demethylase KDM5A is an integral part of the core Notch–RBP-J repressor complex

Robert Liefke; Franz Oswald; Cristobal Alvarado; Dolores Ferres-Marco; Gerhard Mittler; Patrick Rodriguez; Maria Dominguez; Tilman Borggrefe

doi:10.1101/gad.563210

Histone demethylase KDM5A is an integral part of the core Notch–RBP-J repressor complex

¹Max-Planck-Institute of Immunobiology, 79108 Freiburg, Germany;
²Department of Internal Medicine I, University of Ulm, 89081 Ulm, Germany;
³Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas-Universidad Miguel Hernández, Campus de Sant Joan, Alicante, E-03550, Spain

↵4 These authors contributed equally to this work.

Abstract

Timely acquisition of cell fates and the elaborate control of growth in numerous organs depend on Notch signaling. Upon ligand binding, the core transcription factor RBP-J activates transcription of Notch target genes. In the absence of signaling, RBP-J switches off target gene expression, assuring the tight spatiotemporal control of the response by a mechanism incompletely understood. Here we show that the histone demethylase KDM5A is an integral, conserved component of Notch/RBP-J gene silencing. Methylation of histone H3 Lys 4 is dynamically erased and re-established at RBP-J sites upon inhibition and reactivation of Notch signaling. KDM5A interacts physically with RBP-J; this interaction is conserved in Drosophila and is crucial for Notch-induced growth and tumorigenesis responses.

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Footnotes

↵5 Corresponding author.

E-MAIL borggrefe{at}immunbio.mpg.de; FAX 49-761-5108-799.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.563210.
Supplemental material is available at http://www.genesdev.org.
- Received October 21, 2009.
- Accepted January 27, 2010.