{"doi":"10.7554/elife.83951","title":"Carm1-arginine methylation of the transcription factor C/EBPα regulates transdifferentiation velocity","abstract":"Here, we describe how the speed of C/EBPα-induced B cell to macrophage transdifferentiation (BMT) can be regulated, using both mouse and human models. The identification of a mutant of C/EBPα (C/EBPα R35A ) that greatly accelerates BMT helped to illuminate the mechanism. Thus, incoming C/EBPα binds to PU.1, an obligate partner expressed in B cells, leading to the release of PU.1 from B cell enhancers, chromatin closing and silencing of the B cell program. Released PU.1 redistributes to macrophage enhancers newly occupied by C/EBPα, causing chromatin opening and activation of macrophage genes. All these steps are accelerated by C/EBPα R35A , initiated by its increased affinity for PU.1. Wild-type C/EBPα is methylated by Carm1 at arginine 35 and the enzyme’s perturbations modulate BMT velocity as predicted from the observations with the mutant. Increasing the proportion of unmethylated C/EBPα in granulocyte/macrophage progenitors by inhibiting Carm1 biases the cell’s differentiation toward macrophages, suggesting that cell fate decision velocity and lineage directionality are closely linked processes.","journal":"eLife","year":2023,"id":370202,"datarank":0.32931832142716794,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.017402090175192484,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.017402090175192484,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":4,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE204746"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1010074,"name":"Elisabeth Kowenz‐Leutz","orcid":null,"position":1,"is_corresponding":false},{"id":1009602,"name":"Tian V. Tian","orcid":"0000-0002-9906-0980","position":2,"is_corresponding":false},{"id":812598,"name":"Antonios Klonizakis","orcid":"0000-0001-9850-6971","position":3,"is_corresponding":false},{"id":267189,"name":"Jonathan Lerner","orcid":"0000-0002-3513-3191","position":4,"is_corresponding":false},{"id":1009603,"name":"Luísa de Andrés-Aguayo","orcid":"0000-0001-6717-242X","position":5,"is_corresponding":false},{"id":1129729,"name":"Valeriia Sapozhnikova","orcid":null,"position":6,"is_corresponding":false},{"id":1009604,"name":"Clara Berenguer","orcid":"0000-0003-4190-8085","position":7,"is_corresponding":false},{"id":1009605,"name":"Marcos Plana-Carmona","orcid":"0000-0002-1976-7506","position":8,"is_corresponding":false},{"id":1009606,"name":"María Vila-Casadesús","orcid":"0000-0001-6597-7953","position":9,"is_corresponding":false},{"id":1009607,"name":"Romain Bulteau","orcid":"0000-0002-9128-8809","position":10,"is_corresponding":false},{"id":1009608,"name":"Mirko Francesconi","orcid":"0000-0002-8702-0877","position":11,"is_corresponding":false},{"id":998499,"name":"Sandra Peiró","orcid":"0000-0001-9519-3877","position":12,"is_corresponding":false},{"id":2203,"name":"Philipp Mertins","orcid":"0000-0002-2245-528X","position":13,"is_corresponding":false},{"id":98970,"name":"Kenneth S. Zaret","orcid":"0000-0001-8932-3145","position":14,"is_corresponding":false},{"id":1009609,"name":"Achim Leutz","orcid":"0000-0001-8259-927X","position":15,"is_corresponding":false},{"id":1009610,"name":"Thomas Graf","orcid":"0000-0003-2774-4117","position":16,"is_corresponding":false},{"id":1009601,"name":"Guillem Torcal Garcia","orcid":"0000-0002-0843-7296","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T01:15:37.094100Z","pmid":"37365888","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":[]}