Journal Article (Review Article)

DKFZ-2024-00261

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Canalizing cell fate by transcriptional repression.

Lim, B. (First author)DKFZ* ; Domsch, K. ; Mall, M. (Last author)DKFZ* ; Lohmann, I.

2024
EMBO Press Heidelberg

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Please use a persistent id in citations: doi:10.1038/s44320-024-00014-z

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.

Keyword(s): Alternative Fate Repression ; Cell Fate Plasticity ; Cell Identity ; Epigenetic Silencing ; Transcriptional Repressor

Note: ZMBH Alliance / #EA:A340#LA:A340# / 2024 Mar;20(3):144-161

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Contributing Institute(s):

1. A340 NWG Engeneering von Zellidentitäten und Krankheitsmodellen (A340)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2024

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