Cited by 19Genomics and Chromatin DynamicsDevelopmental Biology and Gene RegulationEpigenetics and DNA Methylation

Canalizing cell fate by transcriptional repression

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Lim, Bryce, Domsch, Katrin, Mall, Moritz, Lohmann, Ingrid·2024·Molecular Systems Biology

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.

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Authors
Lim, B., Domsch, K., Mall, M., & Lohmann, I.
Affiliations
  • German Cancer Research Center (DE)
  • Heidelberg University (DE)
Corresponding author
  • Mall, Moritz
  • Lohmann, Ingrid
Venue
Molecular Systems Biology
Published
2024-02-01
Volume
20
Issue
3
Pages
144-161
ISSN
1744-4292 (ISSN-L)
OpenAlex
W4391435778
Cited by
19
References
149
Citations by year
2026: 8 · 2025: 7 · 2024: 4
FWCI
0.78
Type
journal article
Language
en
Open access
Locations
  • Molecular Systems Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Deutsche Forschungsgemeinschaft (504019642, 514206638, LO 844/8-4)
  • EC | ERC | HORIZON EUROPE European Research Council (804710)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
cell fate determination, transcriptional repression, sequence-specific transcription factors, cis-regulatory elements, chromatin accessibility, cellular plasticity, master regulators, cell identity maintenance, developmental gene regulation
MeSH terms
Cell Differentiation, Chromatin, Transcription Factors, Transcriptional Activation, Gene Expression

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