MOZ and Menin-MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor.

ABSTRACT: Gastrointestinal stromal tumor (GIST) is commonly characterized by activating mutations in the receptor tyrosine kinase KIT. Tyrosine kinase inhibitors are the only approved therapy for GIST, and complementary treatment strategies are urgently needed. As GIST lacks oncogene amplification and relies upon an established network of transcription factors, we hypothesized that unique chromatin-modifying enzymes are essential in orchestrating the GIST epigenome. We identified through genome-scale CRISPR screening that MOZ and Menin-MLL chromatin regulatory complexes are cooperative and unique dependencies in GIST. These complexes were enriched at GIST-relevant genes and regulated their transcription. Inhibition of MOZ and Menin-MLL complexes decreased GIST cell proliferation by disrupting intera

SUBMITTER: Hemming ML 

PROVIDER: S-EPMC9453853 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature