Carm1-arginine methylation of the transcription factor C/EBPα regulates transdifferentiation velocity
| Autor: | Torcal Garcia, Guillem, Kowenz-Leutz, Elisabeth, TIAN, TIAN, Klonizakis, Antonis, Lerner, Jonathan, de Andres-Aguayo, Luisa, Vila-Casadesús, Maria, Peiró, Sandra |
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| Přispěvatelé: | Institut Català de la Salut, [Torcal Garcia G, Klonizakis A, De Andres-Aguayo L] Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. [Kowenz-Leutz E] Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. [Tian TV, Vila Casadesus M] Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Lerner J] Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States. [Peiro S] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
Cell Physiological Phenomena::Cell Differentiation [PHENOMENA AND PROCESSES]
Cell Physiological Phenomena::Cell Transdifferentiation [PHENOMENA AND PROCESSES] Cèl·lules B fenómenos químicos::fenómenos bioquímicos::alquilación::metilación [FENÓMENOS Y PROCESOS] Chemical Phenomena::Biochemical Phenomena::Alkylation::Methylation [PHENOMENA AND PROCESSES] Diferenciació cel·lular Ratolins fenómenos fisiológicos celulares::transdiferenciación celular [FENÓMENOS Y PROCESOS] Metilació Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice [ORGANISMS] Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones [ORGANISMOS] fenómenos fisiológicos celulares::diferenciación celular [FENÓMENOS Y PROCESOS] |
| Zdroj: | Scientia |
| Popis: | Developmental biology; Gene regulation; Transcription factor Biologia del desenvolupament; Regulació gènica; Factor de transcripció Biología del desarrollo; Regulación génica; Factor de transcripción 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/EBPαR35A) 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/EBPαR35A, 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. TG was supported by the Center for Genomic Regulation, Barcelona, the Spanish Ministry of Economy, Industry and Competitiveness, (Plan Estatal PID2019-109354GB-100), AGAUR (SGR 006713) and the 4D-Genome European Research Council Synergy grant. KSZ was supported by the NIH grant R01GM36477. We have used ChatGPT to improve parts of the text. |
| Databáze: | OpenAIRE |
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