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- W4301394976 abstract "ABSTRACT Cell fate decisions are driven by lineage-restricted transcription factors but how they are regulated is incompletely understood. The C/EBPα-induced B cell to macrophage transdifferentiation (BMT) is a powerful system to address this question. Here we describe that C/EBPα with a single arginine mutation (C/EBPα R35A ) induces a dramatically accelerated BMT in mouse and human cells. Changes in the expression of lineage-restricted genes occur as early as within 1 hour compared to 18 hours with the wild type. Mechanistically C/EBPα R35A exhibits an increased affinity for PU.1, a bi-lineage transcription factor required for C/EBPα-induced BMT. The complex induces more rapid chromatin accessibility changes and an enhanced relocation (stealing) of PU.1 from B cell to myeloid gene regulatory elements. Arginine 35 is methylated by Carm1 and inhibition of the enzyme accelerates BMT, similar to the mutant. Our data suggest that the relative proportions of methylated and unmethylated C/EBPα in a bipotent progenitor can determine the velocity of cell fate choice and lineage directionality." @default.
- W4301394976 created "2022-10-05" @default.
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- W4301394976 date "2022-10-04" @default.
- W4301394976 modified "2023-10-18" @default.
- W4301394976 title "Carm1 regulates the speed of C/EBPα-induced transdifferentiation by a cofactor stealing mechanism" @default.
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- W4301394976 doi "https://doi.org/10.1101/2022.10.03.510647" @default.
- W4301394976 hasPublicationYear "2022" @default.
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