A Unique Epigenomic Landscape Defines Human Erythropoiesis

Cell Rep. 2019 Sep 10;28(11):2996-3009.e7. doi: 10.1016/j.celrep.2019.08.020.


Mammalian erythropoiesis yields a highly specialized cell type, the mature erythrocyte, evolved to meet the organismal needs of increased oxygen-carrying capacity. To better understand the regulation of erythropoiesis, we performed genome-wide studies of chromatin accessibility, DNA methylation, and transcriptomics using a recently developed strategy to obtain highly purified populations of primary human erythroid cells. The integration of gene expression, DNA methylation, and chromatin state dynamics reveals that stage-specific gene regulation during erythropoiesis is a stepwise and hierarchical process involving many cis-regulatory elements. Erythroid-specific, nonpromoter sites of chromatin accessibility are linked to erythroid cell phenotypic variation and inherited disease. Comparative analyses of stage-specific chromatin accessibility indicate that there is limited early chromatin priming of erythroid genes during hematopoiesis. The epigenome of terminally differentiating erythroid cells defines a distinct subset of highly specialized cells that are vastly dissimilar from other hematopoietic and nonhematopoietic cell types. These epigenomic and transcriptome data are powerful tools to study human erythropoiesis.

Keywords: anemia; chromatin; epigenomic; erythrocyte; erythropoiesis; methylation; trait.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly / genetics*
  • DNA Methylation / genetics
  • Epigenesis, Genetic
  • Erythroid Cells / metabolism*
  • Erythropoiesis / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Hematologic Diseases / genetics
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Multigene Family
  • Polymorphism, Single Nucleotide
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Transcriptome


  • Chromatin