Non-canonical PRC1.1 Targets Active Genes Independent of H3K27me3 and Is Essential for Leukemogenesis

• DOI: 10.1016/j.celrep.2015.12.034
• Publication Date: 2015-12-31T18:53:05Z
• Authors: Vincent van den Boom; Henny Maat; Marjan Geugien; Aida Rodríguez López; Ana M. Sotoca; Jennifer Jaques; Annet Z. Brouwers...; Fabrizia Fusetti; Richard W.J. Groen; Huipin Yuan; Anton C.M. Martens; Hendrik G. Stunne...; Edo Vellenga; Joost H.A. Martens; Jan Jacob Schuringa
• Keywords: Non canonical

Highlights•The non-canonical PRC1.1 complex is critically important for human LSCs•Several members are overexpressed in primary AML•PRC1.1 can bind TSSs the absence of repressive H3K27me3 PRC2 mark•PRC1.1 targets actively transcribed genes involved metabolismSummaryPolycomb proteins classical regulators stem cell self-renewal and lineage commitment frequently deregulated cancer. Here, we find that complex, as identified by mass-spectrometry-based proteomics, leukemic cells. Downmodulation members, like DNA-binding subunit KDM2B, strongly reduces proliferation vitro delays or even abrogates leukemogenesis vivo humanized xenograft models. components significantly AML CD34+ Besides a set targeted PRC1 PRC2, ChIP-seq studies show also binds distinct devoid H3K27me3, suggesting gene-regulatory role independent PRC2. This encompasses metabolism, which have transcriptionally active chromatin profiles. These data indicate controls specific unique biological processes required viability.Graphical abstract