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Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.

Weishaupt, Holger LU ; Sigvardsson, Mikael LU and Attema, Joanne LU (2010) In Blood 115. p.247-256
Abstract
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 miniChIP technology. We show that genes involved in mature hematopoietic cell function associate with distinct chromatin states in stem and progenitor cells, prior to 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.... (More)
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 miniChIP technology. We show that genes involved in mature hematopoietic cell function associate with distinct chromatin states in stem and progenitor cells, prior to 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 over-representation of promoters encoding key regulators of hematopoiesis. Following 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
115
pages
247 - 256
publisher
American Society of Hematology
external identifiers
  • wos:000273622600014
  • pmid:19887676
  • scopus:75649147458
ISSN
1528-0020
DOI
10.1182/blood-2009-07-235176
language
English
LU publication?
yes
id
48d3318a-16e3-4be6-a7be-2acaee38eb15 (old id 1512277)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19887676?dopt=Abstract
date added to LUP
2009-12-01 11:39:46
date last changed
2018-05-29 10:26:08
@article{48d3318a-16e3-4be6-a7be-2acaee38eb15,
  abstract     = {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 miniChIP technology. We show that genes involved in mature hematopoietic cell function associate with distinct chromatin states in stem and progenitor cells, prior to 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 over-representation of promoters encoding key regulators of hematopoiesis. Following 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.},
  author       = {Weishaupt, Holger and Sigvardsson, Mikael and Attema, Joanne},
  issn         = {1528-0020},
  language     = {eng},
  pages        = {247--256},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.},
  url          = {http://dx.doi.org/10.1182/blood-2009-07-235176},
  volume       = {115},
  year         = {2010},
}