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Publication : Opposing roles of polycomb repressive complexes in hematopoietic stem and progenitor cells.

First Author  Majewski IJ Year  2010
Journal  Blood Volume  116
Issue  5 Pages  731-9
PubMed ID  20445021 Mgi Jnum  J:163504
Mgi Id  MGI:4822116 Doi  10.1182/blood-2009-12-260760
Citation  Majewski IJ, et al. (2010) Opposing roles of polycomb repressive complexes in hematopoietic stem and progenitor cells. Blood 116(5):731-9
abstractText  Polycomb group (PcG) proteins are transcriptional repressors with a central role in the establishment and maintenance of gene expression patterns during development. We have investigated the role of polycomb repressive complexes (PRCs) in hematopoietic stem cells (HSCs) and progenitor populations. We show that mice with loss of function mutations in PRC2 components display enhanced HSC/progenitor population activity, whereas mutations that disrupt PRC1 or pleiohomeotic repressive complex are associated with HSC/progenitor cell defects. Because the hierarchical model of PRC action would predict synergistic effects of PRC1 and PRC2 mutation, these opposing effects suggest this model does not hold true in HSC/progenitor cells. To investigate the molecular targets of each complex in HSC/progenitor cells, we measured genome-wide expression changes associated with PRC deficiency, and identified transcriptional networks that are differentially regulated by PRC1 and PRC2. These studies provide new insights into the mechanistic interplay between distinct PRCs and have important implications for approaching PcG proteins as therapeutic targets.
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