Canalizing cell fate by transcriptional repression
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...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2024-02-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s44320-024-00014-z |
| _version_ | 1797272279832330240 |
|---|---|
| author | Bryce Lim Katrin Domsch Moritz Mall Ingrid Lohmann |
| author_facet | Bryce Lim Katrin Domsch Moritz Mall Ingrid Lohmann |
| author_sort | Bryce Lim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:25:07Z |
| format | Article |
| id | doaj.art-4c8d1ce2da324abd8138a54f285ee6a3 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T14:25:07Z |
| publishDate | 2024-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-4c8d1ce2da324abd8138a54f285ee6a32024-03-06T08:06:06ZengSpringer NatureMolecular Systems Biology1744-42922024-02-0120314416110.1038/s44320-024-00014-zCanalizing cell fate by transcriptional repressionBryce Lim0Katrin Domsch1Moritz Mall2Ingrid Lohmann3Cell Fate Engineering and Disease Modeling Group, German Cancer Research Center (DKFZ) and DKFZ-ZMBH AllianceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks - Cluster of ExcellenceCell Fate Engineering and Disease Modeling Group, German Cancer Research Center (DKFZ) and DKFZ-ZMBH AllianceHeidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and Cell Networks - Cluster of ExcellenceAbstract 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.https://doi.org/10.1038/s44320-024-00014-zAlternative Fate RepressionCell IdentityCell Fate PlasticityEpigenetic SilencingTranscriptional Repressor |
| spellingShingle | Bryce Lim Katrin Domsch Moritz Mall Ingrid Lohmann Canalizing cell fate by transcriptional repression Molecular Systems Biology Alternative Fate Repression Cell Identity Cell Fate Plasticity Epigenetic Silencing Transcriptional Repressor |
| title | Canalizing cell fate by transcriptional repression |
| title_full | Canalizing cell fate by transcriptional repression |
| title_fullStr | Canalizing cell fate by transcriptional repression |
| title_full_unstemmed | Canalizing cell fate by transcriptional repression |
| title_short | Canalizing cell fate by transcriptional repression |
| title_sort | canalizing cell fate by transcriptional repression |
| topic | Alternative Fate Repression Cell Identity Cell Fate Plasticity Epigenetic Silencing Transcriptional Repressor |
| url | https://doi.org/10.1038/s44320-024-00014-z |
| work_keys_str_mv | AT brycelim canalizingcellfatebytranscriptionalrepression AT katrindomsch canalizingcellfatebytranscriptionalrepression AT moritzmall canalizingcellfatebytranscriptionalrepression AT ingridlohmann canalizingcellfatebytranscriptionalrepression |