| Literature DB >> 26748712 |
Vincent van den Boom1, Henny Maat1, Marjan Geugien2, Aida Rodríguez López1, Ana M Sotoca3, Jennifer Jaques1, Annet Z Brouwers-Vos1, Fabrizia Fusetti4, Richard W J Groen5, Huipin Yuan6, Anton C M Martens5, Hendrik G Stunnenberg3, Edo Vellenga1, Joost H A Martens3, Jan Jacob Schuringa7.
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 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 set encompasses genes involved in metabolism, which have transcriptionally active chromatin profiles. These data indicate that PRC1.1 controls specific genes involved in unique cell biological processes required for leukemic cell viability.Entities:
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Year: 2015 PMID： 26748712 DOI： 10.1016/j.celrep.2015.12.034
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423