Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment. Academic Article uri icon

Overview

MeSH

  • Adult
  • Binding Sites
  • Cell Differentiation
  • Cell Lineage
  • Comparative Genomic Hybridization
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation
  • Genome, Human
  • Hematopoietic System
  • Humans
  • Models, Biological
  • Promoter Regions, Genetic

MeSH Major

  • DNA Methylation
  • Hematopoietic Stem Cells

abstract

  • DNA methylation has been implicated as an epigenetic component of mechanisms that stabilize cell-fate decisions. Here, we have characterized the methylomes of human female hematopoietic stem/progenitor cells (HSPCs) and mature cells from the myeloid and lymphoid lineages. Hypomethylated regions (HMRs) associated with lineage-specific genes were often methylated in the opposing lineage. In HSPCs, these sites tended to show intermediate, complex patterns that resolve to uniformity upon differentiation, by increased or decreased methylation. Promoter HMRs shared across diverse cell types typically display a constitutive core that expands and contracts in a lineage-specific manner to fine-tune the expression of associated genes. Many newly identified intergenic HMRs, both constitutive and lineage specific, were enriched for factor binding sites with an implied role in genome organization and regulation of gene expression, respectively. Overall, our studies represent an important reference data set and provide insights into directional changes in DNA methylation as cells adopt terminal fates. Copyright © 2011 Elsevier Inc. All rights reserved.

publication date

  • October 7, 2011

has subject area

  • Adult
  • Binding Sites
  • Cell Differentiation
  • Cell Lineage
  • Comparative Genomic Hybridization
  • DNA Methylation
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation
  • Genome, Human
  • Hematopoietic Stem Cells
  • Hematopoietic System
  • Humans
  • Models, Biological
  • Promoter Regions, Genetic

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3412369

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2011.08.026

PubMed ID

  • 21924933

Additional Document Info

start page

  • 17

end page

  • 28

volume

  • 44

number

  • 1