A Unique Epigenomic Landscape Defines Human Erythropoiesis

• Published in: Cell reports (Cambridge) Vol. 28; no. 11; pp. 2996 - 3009.e7
• Main Authors: Schulz, Vincent P., Yan, Hongxia, Lezon-Geyda, Kimberly, An, Xiuli, Hale, John, Hillyer, Christopher D., Mohandas, Narla, Gallagher, Patrick G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.09.2019; Elsevier
• Subjects: anemia; chromatin; epigenomic; erythrocyte; erythropoiesis; methylation; trait; methylation; epigenomic; trait; erythropoiesis; chromatin; anemia; erythrocyte
• ISSN: 2211-1247; 2211-1247
• 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. [Display omitted] •Epigenomic landscape of erythropoiesis reveals stage-specific patterns of regulation•Epigenomic changes in erythropoiesis are linked to erythroid traits and disease genes•Erythroid cells exhibit chromatin accessibility patterns distinct from other cell types Schulz et al. use genome-wide studies of chromatin accessibility, DNA methylation, and transcriptomes in primary human erythroid cells to reveal important characteristics of erythropoiesis. Chromatin accessibility of terminal erythroid differentiation is markedly dissimilar from other hematopoietic cell types. Epigenomic changes are linked to erythroid cell traits and disease genes.