Canalizing cell fate by transcriptional repression

Mol Syst Biol. 2024 Mar;20(3):144-161. doi: 10.1038/s44320-024-00014-z. Epub 2024 Feb 1.

Abstract

Precision in the establishment and maintenance of cellular identities is crucial for the development of multicellular organisms and requires tight regulation of gene expression. While extensive research has focused on understanding cell type-specific gene activation, the complex mechanisms underlying the transcriptional repression of alternative fates are not fully understood. Here, we provide an overview of the repressive mechanisms involved in cell fate regulation. We discuss the molecular machinery responsible for suppressing alternative fates and highlight the crucial role of sequence-specific transcription factors (TFs) in this process. Depletion of these TFs can result in unwanted gene expression and increased cellular plasticity. We suggest that these TFs recruit cell type-specific repressive complexes to their cis-regulatory elements, enabling them to modulate chromatin accessibility in a context-dependent manner. This modulation effectively suppresses master regulators of alternative fate programs and their downstream targets. The modularity and dynamic behavior of these repressive complexes enables a limited number of repressors to canalize and maintain major and minor cell fate decisions at different stages of development.

Keywords: Alternative Fate Repression; Cell Fate Plasticity; Cell Identity; Epigenetic Silencing; Transcriptional Repressor.

Publication types

  • Review

MeSH terms

  • Cell Differentiation / genetics
  • Chromatin* / genetics
  • Gene Expression
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism
  • Transcriptional Activation

Substances

  • Transcription Factors
  • Chromatin