| RRC ID |
11073
|
| Author |
Liefke R, Oswald F, Alvarado C, Ferres-Marco D, Mittler G, Rodriguez P, Dominguez M, Borggrefe T.
|
| Title |
Histone demethylase KDM5A is an integral part of the core Notch-RBP-J repressor complex.
|
| Journal |
Genes Dev
|
| 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.
|
| Volume |
24(6)
|
| Pages |
590-601
|
| Published |
2010-3-15
|
| DOI |
10.1101/gad.563210
|
| PII |
24/6/590
|
| PMID |
20231316
|
| PMC |
PMC2841336
|
| MeSH |
Animals
Cell Line
Cell Line, Tumor
DNA-Binding Proteins / metabolism
Drosophila Proteins / metabolism
Drosophila melanogaster
Histones / metabolism
Humans
Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism*
Jumonji Domain-Containing Histone Demethylases
Mice
Receptors, Notch / metabolism*
Retinoblastoma-Binding Protein 2 / metabolism*
Signal Transduction*
T-Lymphocytes
Ubiquitin-Protein Ligases
|
| IF |
9.527
|
| Times Cited |
111
|
|
WOS Category
|
GENETICS & HEREDITY
DEVELOPMENTAL BIOLOGY
CELL BIOLOGY
|
| Resource |
| Drosophila |
9088R-1
9088R-2 |
