{"doi":"10.1093/jleuko/qiaf159","title":"A critical role of the Erk1/2 downstream targets c-Fos, Egr-1, and Egr-2 in PU.1-driven monocyte development","abstract":"The Ets family transcription factor PU.1 plays multiple roles in hematopoiesis. PU.1 acts in a graded manner to regulate myeloid and lymphoid development with high expression levels promoting monopoiesis and low expression levels instructing B cell fate. It remains incompletely understood how PU.1 promotes monocyte development. In this study, we show that PU.1 activation upregulated, whereas PU.1 knockdown downregulated, the expression of c-Fos, Egr-1, and Egr-2, which are the immediate early response genes of the Erk1/2 pathway and have been shown to promote monopoiesis. A PU.1 mutant defective in c-Jun interaction was unable to upregulate the expression of c-Fos, Egr-1, and Egr-2, indicating that interaction with c-Jun is required for PU.1-mediated upregulation of c-Fos, Egr-1, and Egr-2. We further demonstrate that PU.1 bound to and transcriptionally activated the promoters of c-Fos, Egr-1, and Egr-2. Knockdown of c-Fos or Egr-1 favored neutrophil over monocyte development in response to PU.1 activation, which was associated with increased Gfi1 expression. Notably, PU.1-mediated upregulation of c-Fos, Egr-1, and Egr-2 was blocked upon inhibition of Erk1/2 signaling, which was also associated with an increase in Gfi1 expression and a shift toward neutrophil development at the expense of monopoiesis. Together, these results reveal a novel mechanism by which PU.1 acts to promote monopoiesis and a critical role of the Erk1/2 downstream targets c-Fos, Egr-1 and Egr-2 in PU.1-driven monocyte development.","journal":"Journal of Leukocyte Biology","year":2025,"id":580607,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"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":1303114,"name":"G C Binod","orcid":null,"position":1,"is_corresponding":false},{"id":1492096,"name":"Ariyan Arman Rahman","orcid":null,"position":2,"is_corresponding":false},{"id":1491785,"name":"Fan Dong","orcid":"0009-0005-9251-4520","position":3,"is_corresponding":false},{"id":1492095,"name":"Hafiza Sidra Bashir","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T02:58:43.046112Z","pmid":"41206684","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":[]}