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CBFβ-SMMHC affects genome-wide Polycomb Repressive Complex 1 activity in Acute Myeloid Leukemia

ABSTRACT: 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 CBFβ-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 CBFβ-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. CBFβ-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 CBFβ-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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE128771 | GEO | 2020/01/22

REPOSITORIES: GEO

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RUNX1 and CBFβ-SMMHC transactivate target genes together in abnormal myeloid progenitors for leukemogenesis

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CBFβ-SMMHC affects genome-wide Polycomb Repressive Complex 1 activity in Acute Myeloid Leukemia

Project description:CBFβ-SMMHC affects genome-wide Polycomb Repressive Complex 1 activity in Acute Myeloid Leukemia

| PRJNA528866 | ENA

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