Regeneration Alters Open Chromatin and Cis-Regulatory Landscape of Erythroid Precursors

Stress erythropoiesis elevates the rate of red blood cell (RBC) production as a physiological response to stressors such as anemia or hypoxia. To identify cis-regulatory changes that underlie anemia-specific gene expression and cellular responses, we analyzed chromatin accessibility in populations of cells enriched for red blood cell precursors isolated from mice at a range of time points after anemia induction. The representation of red blood cell trait-associated loci in ATAC-seq data remained durably elevated more than 1 month after anemia resolution. Together, these findings provide a framework to understand the early establishment and late resolution of a regeneration-dependent transcriptome in RBC progenitors and precursors. Overall design: We used ATAC-seq to map chromatin accessibility in populations of cells enriched for red blood cell precursors isolated from mice at a range of time points (0, 1, 3, 7, 14, 21, 35 days) after anemia induced by the red blood cell lysing chemical phenylhydrazine