Biology subjects

Bulteau, R.

Publications and source records attributed to Bulteau, R..

2 recordsLinked to original sources

bioRxiv2022

Carm1 regulates the speed of C/EBPa-induced transdifferentiation by a cofactor stealing mechanism

Cell fate decisions are driven by lineage-restricted transcription factors but how they are regulated is incompletely understood. The C/EBP-induced B cell to macrophage transdifferentiation (BMT) is a powerful system to address this question. Here we describe that C/EBP with a single arginine mutation (C/EBPR35A) 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/EBPR35A exhibits an increased affinity for PU.1, a bi-lineage transcription factor required for C/EBP-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/EBP in a bipotent progenitor can determine the velocity of cell fate choice and lineage directionality.

cell biology↗

bioRxiv2021

Real Age Prediction from the Transcriptome with RAPToR

Transcriptomic data is often affected by uncontrolled variation among samples that can obscure and confound the effects of interest. This is frequently due to unintended differences in developmental stages between samples. The transcriptome itself can be used to estimate developmental progression, but existing methods require many samples and do not estimate a real developmental time. Here we present RAPToR, a simple and precise computational method that estimates the real age of a sample from its transcriptome, exploiting existing time-series data as reference. RAPToR works with whole animal, dissected tissue and single-cell data, for the most common animal models, humans and even for nonmodel organisms lacking reference data. We show RAPToR estimated age improves differential expression analysis by recovering the signal of interest when confounded with age. RAPToR will be especially useful in large scale single organism profiling because it eliminates the need for accurate staging or synchronization before profiling.

bioinformatics↗