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Chromatin-mediated translational control is essential for neural cell fate specification.
Hwang, Dong-Woo; Jaganathan, Anbalagan; Shrestha, Padmina; Jin, Ying; El-Amine, Nour; Wang, Sidney H; Hammell, Molly; Mills, Alea A.
Afiliación
  • Hwang DW; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
  • Jaganathan A; Graduate Program in Genetics, Stony Brook University, Stony Brook, NY, USA.
  • Shrestha P; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
  • Jin Y; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
  • El-Amine N; Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, NY, USA.
  • Wang SH; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
  • Hammell M; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
  • Mills AA; Center for Human Genetics, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Life Sci Alliance ; 1(4): e201700016, 2018 Aug.
Article en En | MEDLINE | ID: mdl-30456361
Neural cell fate specification is a multistep process in which stem cells undergo sequential changes in states, giving rise to particular lineages such as neurons and astrocytes. This process is accompanied by dynamic changes of chromatin and in transcription, thereby orchestrating lineage-specific gene expression programs. A pressing question is how these events are interconnected to sculpt cell fate. We show that altered chromatin due to loss of the chromatin remodeler Chd5 causes neural stem cell activation to occur ahead of time. This premature activation is accompanied by transcriptional derepression of ribosomal subunits, enhanced ribosome biogenesis, and increased translation. These untimely events deregulate cell fate decisions, culminating in the generation of excessive numbers of astrocytes at the expense of neurons. By monitoring the proneural factor Mash1, we further show that translational control is crucial for appropriate execution of cell fate specification, thereby providing new insight into the interplay between transcription and translation at the initial stages of neurogenesis.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Life Sci Alliance Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Life Sci Alliance Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos