Identification and characterization of enhancer elements controlling cell type-specific and signalling dependent chromatin programming during hematopoietic development.
Identification and characterization of enhancer elements controlling cell type-specific and signalling dependent chromatin programming during hematopoietic development.
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DOI：
10.21037/sci-2023-011
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发表时间：
2023
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从一个受精卵发育成多细胞生物体需要差异地执行我们DNA中编码的信息。这个复杂的过程是由转录因子与染色质环境的相互作用调节的，这两者都提供了维持细胞类型特异性基因表达模式的表观遗传信息。此外，转录因子和它们的靶基因形成了巨大的相互作用的基因调控网络，这些网络可以非常稳定。然而，所有发育过程都起源于多能前体细胞类型。因此，从这样的细胞产生终末分化的细胞需要细胞命运的连续变化，这意味着必须打开与下一分化阶段相关的基因，并且必须关闭不再相关的基因。细胞命运改变的刺激来源于外部信号，其启动细胞内过程的级联反应，最终终止于基因组，导致基因表达的变化和替代基因调控网络的发展。发育轨迹如何在基因组中编码，以及内在和外在过程之间的相互作用如何调节发育是发育生物学的主要问题之一。造血系统的发育长期以来一直是理解基因调控网络的变化如何驱动各种血细胞类型分化的模型。在这篇综述中，我们重点介绍了主要的信号和转录因子，以及它们如何在染色质编程和基因表达控制水平上整合。我们还强调了最近的研究确定的顺式调控元件，如增强子在全球范围内，并解释他们的发育活动是如何调节的细胞类型特异性和普遍存在的转录因子与外源信号的合作。
The development of multi-cellular organisms from a single fertilized egg requires to differentially execute the information encoded in our DNA. This complex process is regulated by the interplay of transcription factors with a chromatin environment, both of which provide the epigenetic information maintaining cell-type specific gene expression patterns. Moreover, transcription factors and their target genes form vast interacting gene regulatory networks which can be exquisitely stable. However, all developmental processes originate from pluripotent precursor cell types. The production of terminally differentiated cells from such cells, therefore, requires successive changes of cell fates, meaning that genes relevant for the next stage of differentiation must be switched on and genes not relevant anymore must be switched off. The stimulus for the change of cell fate originates from extrinsic signals which set a cascade of intracellular processes in motion that eventually terminate at the genome leading to changes in gene expression and the development of alternate gene regulatory networks. How developmental trajectories are encoded in the genome and how the interplay between intrinsic and extrinsic processes regulates development is one of the major questions in developmental biology. The development of the hematopoietic system has long served as model to understand how changes in gene regulatory networks drive the differentiation of the various blood cell types. In this review, we highlight the main signals and transcription factors and how they are integrated at the level of chromatin programming and gene expression control. We also highlight recent studies identifying the cis-regulatory elements such as enhancers at the global level and explain how their developmental activity is regulated by the cooperation of cell-type specific and ubiquitous transcription factors with extrinsic signals.