Chromatin-mediated translational control is essential for neural cell fate specification

Hwang, D. W., Jaganathan, A., Shrestha, P., Jin, Y., El-Amine, N., Wang, S. H., Hammell, M., Mills, A. A. (August 2018) Chromatin-mediated translational control is essential for neural cell fate specification. Life Sci Alliance, 1 (4). e201700016. ISSN 2575-1077

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URL: https://www.ncbi.nlm.nih.gov/pubmed/30456361
DOI: 10.26508/lsa.201700016

Abstract

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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromatin remodeling
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > translation
CSHL Authors:
Communities: CSHL labs > Hammell M. lab
CSHL labs > Mills lab
Depositing User: Matthew Dunn
Date: 23 August 2018
Date Deposited: 29 Nov 2018 19:56
Last Modified: 29 Nov 2018 19:56
PMCID: PMC6238594
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37477

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