Non-canonical PRC1.1 targets active genes independent of H3K27me3 and is essential for leukemogenesis

ABSTRACT: Polycomb proteins are classical regulators of stem cell self-renewal and cell lineage commitment and are frequently deregulated in cancer. Here we find that the non-canonical PRC1.1 complex, as identified by mass spectrometry-based proteomics, is critically important for human leukemic stem cells. Downmodulation of PRC1.1 complex members, like the DNA-binding subunit KDM2B, strongly reduces cell proliferation in vitro and delays or even abrogates leukemogenesis in vivo in humanized xenograft models. PRC1.1 components are significantly overexpressed in primary AML CD34+ cells. Besides a set of genes that is co-targeted by PRC1 and PRC2, ChIP-seq studies show that PRC1.1 also binds a distinct set of genes that are devoid of H3K27me3 suggesting a gene regulatory role independent of PRC2. This

ORGANISM(S): Homo sapiens

SUBMITTER: Joost Martens 

PROVIDER: E-GEOD-54580 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress