Methylation of a lineage-instructive transcription factor acts as a cell fate switch

Torcal Garcia, Guillem

Methylation of a lineage-instructive transcription factor acts as a cell fate switch

Document Type

Doctoral thesis
Published Version

Author

Torcal Garcia, Guillem

Director

Graf, T. (Thomas)

Publication Date

2022-02-10

Pages

256 p.

License

Citation

Torcal Garcia, G. Methylation of a lineage-instructive transcription factor acts as a cell fate switch. 2022. handle: http://hdl.handle.net/10803/673532

This citation was generated automatically.

Doctoral program

Programa de doctorat en Biomedicina

Abstract

Lineage-instructive transcription factors orchestrate cell fate decisions by regulating gene expression programs. However, how their function is regulated throughout development is poorly understood. C/EBPα is a transcription factor that has been shown to play a key role in several cell fate decisions of several tissues, including myelopoiesis, adipogenesis and early embryo development. The protein arginine methyltransferase Carm1 has also been described to play a role in cell specification during various developmental processes, but a connection to C/EBPα has not been established. In this Thesis, we investigated the link between the two proteins in cell fate decisions. We found that arginine 35 of C/EBPα is a key target of Carm1 methylation, and that this post-translational modification alters the biological properties of the factor and acts as a cell fate switch during myelopoiesis, adipogenesis and the first cell fate decision between pluripotency and trophectoderm in early embryos.
Los factores de transcripción instructores de linaje orquestan decisiones de identidad celular a través de la regulación de programas de expresión génica. Sin embargo, cómo su función está regulada durante el desarrollo todavía se desconoce. C/EBPα es un factor de transcripción que juega un papel clave en varias decisiones de identidad celular, incluyendo mielopoiesis, adipogénesis y el desarrollo embrionario temprano. La metiltransferasa de argininas Carm1 también está involucrada en los mismos procesos, pero todavía no se ha descrito una posible conexión con C/EBPα. En esta Tesis, hemos investigado la conexión entre éstas dos proteínas en decisiones de identidad celular. Hemos descubierto que la arginina 35 de C/EBPα es un blanco clave para la metilación por Carm1, y está modificación postraduccional altera las propiedades biológicas del factor y actúa como un interruptor de identidad celular en mielopoiesis, adipogénesis y en la primera decisión entre pluripotencia y trofectodermo en el embrión.

Keywords

Cell fate decisions, Hematopoiesis, Embryo development, Adipogenesis, Post-translational modifications, Decisions d'identitat cel.lular, Hematopoesi, Desenvolupament embrionari, Adipogènesi, Modificacions post-traduccionals