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Canalizing cell fate by transcriptional repression.
Lim, Bryce; Domsch, Katrin; Mall, Moritz; Lohmann, Ingrid.
Afiliación
  • Lim B; Cell Fate Engineering and Disease Modeling Group, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
  • Domsch K; HITBR Hector Institute for Translational Brain Research gGmbH, 69120, Heidelberg, Germany.
  • Mall M; Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159, Mannheim, Germany.
  • Lohmann I; Heidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks - Cluster of Excellence, Heidelberg, Germany.
Mol Syst Biol ; 20(3): 144-161, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38302581
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Cromatina Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Syst Biol Asunto de la revista: BIOLOGIA MOLECULAR / BIOTECNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Cromatina Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Syst Biol Asunto de la revista: BIOLOGIA MOLECULAR / BIOTECNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido