DOT1L stimulates MYC/Mondo transcription factor activity by promoting its degradation cycle on chromatin

• DOI: 10.1101/2024.02.06.579191
• Publication Date: 2024-02-08T04:55:18Z
• Authors: Gian P. Sepulveda; Ekaterina S. Gush...; Alexandra Mora-Ma...; Ruben Esse; Iana Nikorich; Ainhoa Ceballos; Julian Kwan; Benjamin C. Blum; Prakruti Dholiya; Andrew Emili; Valentina Perissi; Maria D. Cardamone; Alla Grishok
• Keywords: Transcription

SUMMARY The proto-oncogene c-MYC is a key representative of the MYC transcription factor network regulating growth and metabolism. MML-1 (Myc- Mondo-like) its homolog in C. elegans . functional molecular cooperation between H3 lysine 79 methyltransferase DOT1L was demonstrated several human cancer types, we have earlier discovered connection DOT-1.1. Here, demonstrate critical role DOT1L/DOT-1.1 c-MYC/MML-1 target genes genome-wide by ensuring removal “spent” factors from chromatin nuclear proteasome. Moreover, uncover previously unrecognized proteolytic activity DOT1L, which may facilitate turnover. This new mechanism regulation lead to development approaches for treatment.