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Citation
Xu, T., Park, S.S., Giaimo, B.D., Hall, D., Ferrante, F., Ho, D.M., Hori, K., Anhezini, L., Ertl, I., Bartkuhn, M., Zhang, H., Milon, E., Ha, K., Conlon, K.P., Kuick, R., Govindarajoo, B., Zhang, Y., Sun, Y., Dou, Y., Basrur, V., Elenitoba-Johnson, K.S., Nesvizhskii, A.I., Ceron, J., Lee, C.Y., Borggrefe, T., Kovall, R.A., Rual, J.F. (2017). RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1.  EMBO J. 36(21): 3232--3249.
FlyBase ID
FBrf0237076
Publication Type
Research paper
Abstract

Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. Upon ligand binding, the Notch intracellular domain (NOTCH ICD) translocates into the nucleus and forms a complex with the transcription factor RBPJ (also known as CBF1 or CSL) to activate expression of Notch target genes. In the absence of a Notch signal, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 (also known as MBT1) as a novel RBPJ interactor. L3MBTL3 competes with NOTCH ICD for binding to RBPJ In the absence of NOTCH ICD, RBPJ recruits L3MBTL3 and the histone demethylase KDM1A (also known as LSD1) to the enhancers of Notch target genes, leading to H3K4me2 demethylation and to transcriptional repression. Importantly, in vivo analyses of the homologs of RBPJ and L3MBTL3 in Drosophila melanogaster and Caenorhabditis elegans demonstrate that the functional link between RBPJ and L3MBTL3 is evolutionarily conserved, thus identifying L3MBTL3 as a universal modulator of Notch signaling in metazoans.

PubMed ID
PubMed Central ID
PMC5666606 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    EMBO J.
    Title
    The EMBO Journal
    Publication Year
    1982-
    ISBN/ISSN
    0261-4189
    Data From Reference
    Aberrations (1)
    Alleles (7)
    Genes (7)
    Physical Interactions (2)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (2)
    Transgenic Constructs (4)