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

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Liefke,  Robert
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Mittler,  Gerhard
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Rodriguez,  Patrick
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Borggrefe,  Tilman
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Liefke, R., Oswald, F., Alvarado, C., Ferres-Marco, D., Mittler, G., Rodriguez, P., et al. (2010). Histone demethylase KDM5A is an integral part of the core Notch-RBP-J repressor complex. Genes & Development, 24, 590-601.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-8EBF-E
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.