| Autor: |
Guillem Torcal Garcia, Elisabeth Kowenz-Leutz, Tian V Tian, Antonis Klonizakis, Jonathan Lerner, Luisa De Andres-Aguayo, Valeriia Sapozhnikova, Clara Berenguer, Marcos Plana Carmona, Maria Vila Casadesus, Romain Bulteau, Mirko Francesconi, Sandra Peiro, Philipp Mertins, Kenneth Zaret, Achim Leutz, Thomas Graf |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 12 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.83951 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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