Liefke R, Oswald F, Alvarado C, Ferres-Marco D, Mittler G, Rodriguez P, Dominguez M, Borggrefe T

Max-Planck-Institute of Immunobiology, Freiburg, Germany.

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.

Mesh Terms:
Animals, Cell Line, Cell Line, Tumor, DNA-Binding Proteins, Drosophila Proteins, Drosophila melanogaster, Histones, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Mice, Receptors, Notch, Retinoblastoma-Binding Protein 2, Signal Transduction, T-Lymphocytes

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