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RBPJ / CBF 1 interacts with L3 MBTL 3/ MBT 1 to promote repression of Notch signaling via histone demethylase KDM 1A/ LSD 1
Author(s) -
Xu Tao,
Park SungSoo,
Giaimo Benedetto Daniele,
Hall Daniel,
Ferrante Francesca,
Ho Diana M,
Hori Kazuya,
Anhezini Lucas,
Ertl Iris,
Bartkuhn Marek,
Zhang Honglai,
Milon Eléna,
Ha Kimberly,
Conlon Kevin P,
Kuick Rork,
Govindarajoo Brandon,
Zhang Yang,
Sun Yuqing,
Dou Yali,
Basrur Venkatesha,
ElenitobaJohnson Kojo SJ,
Nesvizhskii Alexey I,
Ceron Julian,
Lee ChengYu,
Borggrefe Tilman,
Kovall Rhett A,
Rual JeanFrançois
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201796525
Subject(s) - psychological repression , microbiology and biotechnology , biology , biochemistry , gene , gene expression
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 CBF 1 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 L3 MBTL 3 (also known as MBT 1) as a novel RBPJ interactor. L3 MBTL 3 competes with NOTCH ICD for binding to RBPJ . In the absence of NOTCH ICD , RBPJ recruits L3 MBTL 3 and the histone demethylase KDM 1A (also known as LSD 1) 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 L3 MBTL 3 in Drosophila melanogaster and Caenorhabditis elegans demonstrate that the functional link between RBPJ and L3 MBTL 3 is evolutionarily conserved, thus identifying L3 MBTL 3 as a universal modulator of Notch signaling in metazoans.