Histone demethylase KDM5A is an integral part of the core Notch-RBP-J repressor complex.
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
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
Genes Dev.
Date: Mar. 15, 2010
PubMed ID: 20231316
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