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

被引：109

作者：

Majewski, Ian J. ^{[1
,2
]}

Ritchie, Matthew E. ^{[3
]}

Phipson, Belinda ^{[3
]}

Corbin, Jason ^{[1
,2
]}

Pakusch, Miha ^{[1
]}

Ebert, Anja ^{[4
]}

Busslinger, Meinrad ^{[4
]}

Koseki, Haruhiko ^{[5
]}

Hu, Yifang ^{[3
]}

Smyth, Gordon K. ^{[3
]}

Alexander, Warren S. ^{[2
,6
]}

Hilton, Douglas J. ^{[1
,6
]}

Blewitt, Marnie E. ^{[1
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Div Mol Med, Parkville, Vic 3052, Australia

[2] Walter & Eliza Hall Inst Med Res, Canc & Haematol Div, Parkville, Vic 3052, Australia

[3] Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic 3052, Australia

[4] Inst Mol Pathol, A-1030 Vienna, Austria

[5] RIKEN Res Ctr Allergy & Immunol, Yokohama, Kanagawa, Japan

[6] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia

来源：

BLOOD | 2010年 / 116卷 / 05期

基金：

英国医学研究理事会;

关键词：

HISTONE METHYLTRANSFERASE ACTIVITY; H3; LYSINE-27; METHYLATION; IN-VIVO; DEVELOPMENTAL REGULATORS; TARGETED DISRUPTION; H2A UBIQUITINATION; X-INACTIVATION; GROUP PROTEINS; GENE; EZH2;

D O I：

10.1182/blood-2009-12-260760

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2010; 116(5):731-739)

引用

页码：731 / 739

页数：9

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