Opposing roles of polycomb repressive complexes in hematopoietic stem and progenitor cells
Abstract
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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Applying genas to a microarray study looking at the relationship between PRC1 and PRC2 facilitated the discovery of the opposing roles of these two complexes.
“applying genas to a microarray study looking at the relationship between polycomb repressor complex (PRC) 1 and PRC2 facilitated the discovery of the opposing roles of these two complexes (51).”
From limma powers differential expression analyses for RNA-sequencing and microarray studies (2015) · cites this paper as [51]
EZH2, EED, or SUZ12 loss-of-function mutations are related to increased activity of HSCs and progenitor cells.
“EZH2, EED, or SUZ12 loss-of-function mutations are related to the increased activity of hematologic stem cells (HSCs) and progenitor cells [153].”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [153]
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- Authors
- Majewski, I. J., Ritchie, M. E., Phipson, B., Corbin, J., Pakusch, M., Ebert, A., Busslinger, M., Koseki, H., Hu, Y., Smyth, G. K., Alexander, W. S., Hilton, D. J., & Blewitt, M. E.
- Affiliations
- Molecular Medicine Division,
- Walter and Eliza Hall Institute of Medical Research (AU)
- Research Institute of Molecular Pathology (AT)
- RIKEN (JP)
- The University of Melbourne (AU)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-08-05
- Volume
- 116
- Issue
- 5
- Pages
- 731-739
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2046417042
- Cited by
- 135
- References
- 54
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 8 · 2022: 4 · 2021: 12 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 13 · 2015: 12 · 2014: 11 · 2013: 13 · 2012: 22
- FWCI
- 9.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- polycomb repressive complex, hematopoietic stem cells, hematopoietic progenitor cells, PRC1, polycomb repressive complex 2, transcriptional repression, gene expression profiling, transcriptional regulatory networks, loss-of-function mutations
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, Animals, Hematopoietic Stem Cells, Mice, Inbred C57BL, Mutation, Phenotype, Histone-Lysine N-Methyltransferase, Radiation Chimera, Repressor Proteins, Stem Cells, Transcription, Genetic, Bone Marrow Transplantation, Gene Expression Regulation, Developmental, Gene Expression Profiling, RNA Interference, Multiprotein Complexes, YY1 Transcription Factor, Mice, Gene Knockdown Techniques, Polycomb-Group Proteins, Polycomb Repressive Complex 2
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