RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1
View/ Open
Author
Xu, Tao
Park, Sung‐Soo
Giaimo, Benedetto Daniele
Hall, Daniel
Ferrante, Francesca
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
Elenitoba‐Johnson, Kojo SJ
Nesvizhskii, Alexey I
Ceron, Julian
Lee, Cheng‐Yu
Borggrefe, Tilman
Kovall, Rhett A
Rual, Jean‐François
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.15252/embj.201796525Metadata
Show full item recordCitation
Xu, T., S. Park, B. D. Giaimo, D. Hall, F. Ferrante, D. M. Ho, K. Hori, et al. 2017. “RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1.” The EMBO Journal 36 (21): 3232-3249. doi:10.15252/embj.201796525. http://dx.doi.org/10.15252/embj.201796525.Abstract
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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666606/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492920
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)