通过转录抑制改变细胞命运

IF 8.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Systems Biology Pub Date : 2024-03-01 Epub Date: 2024-02-01 DOI:10.1038/s44320-024-00014-z
Bryce Lim, Katrin Domsch, Moritz Mall, Ingrid Lohmann
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引用次数: 0

摘要

精确建立和维持细胞特性对于多细胞生物体的发育至关重要,需要对基因表达进行严格调控。虽然大量研究集中于了解细胞类型特异性基因的激活,但对替代性命运转录抑制的复杂机制还不完全了解。在此,我们概述了细胞命运调控所涉及的抑制机制。我们讨论了负责抑制替代命运的分子机制,并强调了序列特异性转录因子(TFs)在这一过程中的关键作用。这些转录因子的耗竭会导致不需要的基因表达和细胞可塑性的增加。我们认为,这些转录因子将细胞类型特异性抑制复合物招募到它们的顺式调控元件上,使它们能够以依赖于上下文的方式调节染色质的可及性。这种调节有效地抑制了替代命运程序的主调节因子及其下游靶标。这些抑制复合体的模块化和动态行为使数量有限的抑制因子能够在发育的不同阶段控制和维持主要和次要细胞命运的决定。
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Canalizing cell fate by transcriptional repression.

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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来源期刊
Molecular Systems Biology
Molecular Systems Biology 生物-生化与分子生物学
CiteScore
18.50
自引率
1.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems. Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.
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