Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysis

Joanne L. Attema, Peter Papathanasiou, E. Camilla Forsberg, Jian Xu, Stephen T. Smale, Irving L. Weissman

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

Hematopoietic stem cells (HSC) produce all blood cell lineages by virtue of their capacity to self-renew and differentiate into progenitors with decreasing cellular potential. Recent studies suggest that epigenetic mechanisms play an important role in controlling stem cell potency and cell fate decisions. To investigate this hypothesis in HSC, we have modified the conventional chromatin immunoprecipitation assay allowing for the analysis of 50,000 prospectively purified stem and progenitor cells. Together with bisulfite sequencing analysis, we found that methylated H3K4 and AcH3 and unmethylated CpG dinucleotides colocalize across defined regulatory regions of lineage-affiliated genes in HSC. These active epigenetic histone modifications either accumulated or were replaced by increased DNA methylation and H3K27 trimethylation in committed progenitors consistent with gene expression. We also observed bivalent histone modifications at a lymphoid-affiliated gene in HSC and downstream transit-amplifying progenitors. Together, these data support a model in which epigenetic modifications serve as an important mechanism to control HSC multipotency.

Original languageEnglish (US)
Pages (from-to)12371-12376
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number30
DOIs
StatePublished - Jul 24 2007

Keywords

  • Chromatin
  • Gene expression
  • Hematopoiesis

ASJC Scopus subject areas

  • General

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