{"doi":"10.1016/j.celrep.2020.107993","title":"ATF4 Regulates MYB to Increase γ-Globin in Response to Loss of β-Globin","abstract":"β-Hemoglobinopathies can trigger rapid production of red blood cells in a process known as stress erythropoiesis. Cellular stress prompts differentiating erythroid precursors to express high levels of fetal γ-globin. However, the mechanisms underlying γ-globin production during cellular stress are still poorly defined. Here, we use CRISPR-Cas genome editing to model the stress caused by reduced levels of adult β-globin. We find that decreased β-globin is sufficient to induce robust re-expression of γ-globin, and RNA sequencing (RNA-seq) of differentiating isogenic erythroid precursors implicates ATF4 as a causal regulator of this response. ATF4 binds within the HBS1L-MYB intergenic enhancer and regulates expression of MYB, a known γ-globin regulator. Overall, the reduction of ATF4 upon β-globin knockout decreases the levels of MYB and BCL11A. Identification of ATF4 as a key regulator of globin compensation adds mechanistic insight to the poorly understood phenomenon of stress-induced globin compensation and could inform strategies to treat hemoglobinopathies.","journal":"Cell Reports","year":2020,"id":93828,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":453031,"name":"Markus Schröder","orcid":"0000-0001-5942-1254","position":1,"is_corresponding":false},{"id":468742,"name":"Gautier Stehli","orcid":null,"position":2,"is_corresponding":false},{"id":468743,"name":"Marija Banović","orcid":null,"position":3,"is_corresponding":false},{"id":273395,"name":"Stacia K. Wyman","orcid":"0000-0002-8937-8397","position":4,"is_corresponding":false},{"id":287026,"name":"Rachel J. Lew","orcid":null,"position":5,"is_corresponding":false},{"id":468032,"name":"Matteo Bordi","orcid":"0000-0001-8207-8546","position":6,"is_corresponding":false},{"id":327003,"name":"Benjamin G. Gowen","orcid":"0000-0002-1111-3284","position":7,"is_corresponding":false},{"id":419791,"name":"Mark A. DeWitt","orcid":"0000-0001-8784-0026","position":8,"is_corresponding":false},{"id":233291,"name":"Jacob E. Corn","orcid":"0000-0002-7798-5309","position":9,"is_corresponding":false},{"id":468741,"name":"Mandy Boontanrart","orcid":null,"position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-18T22:31:34.149524Z","pmid":"32755585","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":[]}