{"doi":"10.1101/gr.279949.124","title":"Regeneration alters open chromatin and<i>cis</i>-regulatory landscape of erythroid precursors","abstract":"Stress erythropoiesis elevates the rate of red blood cell (RBC) production as a physiological response to stressors such as anemia or hypoxia. In acute anemia, RBC progenitors and precursors temporarily rewire their transcriptome, up- and downregulating hundreds of genes to accelerate the production of mature RBCs. Effective regeneration requires communication between critical cytokine signals (e.g., BMP4) and cis -regulatory elements on chromatin which coordinate transcriptional changes. 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. Early in the anemia response, chromatin is transiently open at AP-1-containing regions, correlated with increased Jun and Fos transcript/protein levels. Jun knockdown ex vivo decreases the percentage of KIT + erythroid precursors after anemia induction. We observe a second rewiring event at time points consistent with anemia resolution, involving repression of GATA factor-accessible regions and activation of ETS factor-accessible regions. In both mouse in vivo models and human CD34 + cells stimulated with BMP4, accessibility changes at regions with prior associations to human blood phenotypes. Dozens of BMP4- and anemia-activated loci are sensitive to natural human variation. The representation of red blood cell trait–associated loci in ATAC-seq data remains 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 precursors.","journal":"Genome Research","year":2025,"id":555207,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9426,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE275430"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1095633,"name":"Venkatasai Rahul Dogiparthi","orcid":null,"position":1,"is_corresponding":false},{"id":805082,"name":"Hannah L. Harris","orcid":"0000-0001-9321-8751","position":2,"is_corresponding":false},{"id":999291,"name":"Suhita Ray","orcid":"0000-0003-0887-6640","position":3,"is_corresponding":false},{"id":355052,"name":"Avik Choudhuri","orcid":null,"position":4,"is_corresponding":false},{"id":354451,"name":"Song Yang","orcid":"0000-0002-3064-3141","position":5,"is_corresponding":false},{"id":354455,"name":"Yi Zhou","orcid":"0000-0003-0935-1635","position":6,"is_corresponding":false},{"id":49576,"name":"Leonard I. Zon","orcid":"0000-0003-0860-926X","position":7,"is_corresponding":false},{"id":415756,"name":"M. Jordan Rowley","orcid":"0000-0002-5135-9596","position":8,"is_corresponding":false},{"id":999294,"name":"Kyle J. Hewitt","orcid":"0000-0003-1946-625X","position":9,"is_corresponding":false},{"id":999292,"name":"Yichao Zhou","orcid":"0000-0003-2381-3365","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:54:59.329539Z","pmid":"40456602","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}