PLX213477

GSE128771: CBF-SMMHC affects genome-wide Polycomb Repressive Complex 1 activity in Acute Myeloid Leukemia

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Polycomb activity is frequently altered in acute leukaemia through mutation or deletion of Polycomb Repressive Complex (PRC) components. Alterations in PRC-interacting factors such as the Core Binding Factor (CBF) complex should also affect leukemia biology, even if PRC composition is normal. We report that the acute myeloid leukemia (AML)-associated CBF-SMMHC fusion oncoprotein physically interacts with the PRC1 complex, and that these factors co-localize across the AML genome in a PRC2-independent manner. Depletion of CBF-SMMHC caused increases in genome-wide PRC1 binding and an altered association between PRC1 and RUNX1. Overall, PRC1 was more likely to be associated with active genes. CBF-SMMHC depletion had variable transcriptional effects, including significant reductions in expression of PRC1-bound ribosomal loci. Our results expand on the recently reported localized effect of CBF-SMMHC on RUNX1-mediated recruitment of PRC1 at MYC enhancer elements, providing evidence that the oncoprotein diversely affects Polycomb recruitment and transcriptional regulation across the entire AML genome. SOURCE: Joost Martens Radboud University