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Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells
Lund University.
Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology . Linköping University, Faculty of Health Sciences.
Lund University.
2010 (English)In: BLOOD, ISSN 0006-4971, Vol. 115, no 2, 247-256 p.Article in journal (Refereed) Published
Abstract [en]

Heritable epigenetic signatures are proposed to serve as an important regulatory mechanism in lineage fate determination. To investigate this, we profiled chromatin modifications in murine hematopoietic stem cells, lineage-restricted progenitors, and CD4(+) T cells using modified genome-scale mini-chromatin immunoprecipitation technology. We show that genes involved in mature hematopoietic cell function associate with distinct chromatin states in stem and progenitor cells, before their activation or silencing upon cellular maturation. Many lineage-restricted promoters are associated with bivalent histone methylation and highly combinatorial histone modification patterns, which may determine their selective priming of gene expression during lineage commitment. These bivalent chromatin states are conserved in mammalian evolution, with a particular overrepresentation of promoters encoding key regulators of hematopoiesis. After differentiation into progenitors and T cells, activating histone modifications persist at transcriptionally repressed promoters, suggesting that these transcriptional programs might be reactivated after lineage restriction. Collectively, our data reveal the epigenetic framework that underlies the cell fate options of hematopoietic stem cells.

Place, publisher, year, edition, pages
2010. Vol. 115, no 2, 247-256 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-53699DOI: 10.1182/blood-2009-07-235176OAI: diva2:291251
Available from: 2010-02-01 Created: 2010-02-01 Last updated: 2010-02-01

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Sigvardsson, Mikael
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Experimental Hematology Faculty of Health Sciences
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ReferencesLink to record
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