Activating mutations in NOTCH1, an essential regulator of T cell development, 
are frequently found in human T cell acute lymphoblastic leukemia (T-ALL). 
Despite important advances in our understanding of Notch signal transduction, 
the regulation of Notch functions in the nucleus remains unclear. Using 
immunoaffinity purification, we identified NOTCH1 nuclear partners in T-ALL 
cells and showed that, beyond the well-characterized core activation complex 
(ICN1-CSL-MAML1), NOTCH1 assembles a multifunctional complex containing the 
transcription coactivator AF4p12, the PBAF nucleosome remodeling complex, and 
the histone demethylases LSD1 and PHF8 acting through their demethylase activity 
to promote epigenetic modifications at Notch-target genes. Remarkably, LSD1 
functions as a corepressor when associated with CSL-repressor complex and as a 
NOTCH1 coactivator upon Notch activation. Our work provides new insights into 
the molecular mechanisms that govern Notch transcriptional activity and 
represents glimpse into NOTCH1 interaction landscape, which will help in 
deciphering mechanisms of NOTCH1 functions and regulation.