Generation of Single-Cell Transcript Variability by Repression.

Curr Biol

Laboratory for Molecular Cell Biology and Division of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address:

Published: June 2017

AI Article Synopsis

  • Gene expression levels can vary widely among similar cells, impacting cell fate diversity in development and disease.
  • Mechanisms behind this expression variability are not well understood; however, research shows that during Dictyostelium differentiation, variability is mainly caused by gene repression rather than activation.
  • This research suggests that variability results from how often genes are transcribed, rather than how much is produced, highlighting that differences among cells stem from fundamental transcription regulation processes.

Article Abstract

Gene expression levels vary greatly within similar cells, even within clonal cell populations [1]. These spontaneous expression differences underlie cell fate diversity in both differentiation and disease [2]. The mechanisms responsible for generating expression variability are poorly understood. Using single-cell transcriptomics, we show that transcript variability emerging during Dictyostelium differentiation is driven predominantly by repression rather than activation. The increased variability of repressed genes was observed over a broad range of expression levels, indicating that variability is actively imposed and not a passive statistical effect of the reduced numbers of molecules accompanying repression. These findings can be explained by a simple model of transcript production, with expression controlled by the frequency, rather than the magnitude, of transcriptional firing events. Our study reveals that the generation of differences between cells can be a direct consequence of the basic mechanisms of transcriptional regulation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483230PMC
http://dx.doi.org/10.1016/j.cub.2017.05.028DOI Listing

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