Montecino Martin, Carrasco Margarita E, Nardocci Gino
Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences and FONDAP Center for Genome Regulation, Universidad Andres Bello, Santiago, Chile.
Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
Front Cell Dev Biol. 2021 Jan 8;8:611197. doi: 10.3389/fcell.2020.611197. eCollection 2020.
Within the eukaryotic nucleus the genomic DNA is organized into chromatin by stably interacting with the histone proteins as well as with several other nuclear components including non-histone proteins and non-coding RNAs. Together these interactions distribute the genetic material into chromatin subdomains which can exhibit higher and lower compaction levels. This organization contributes to differentially control the access to genomic sequences encoding key regulatory genetic information. In this context, epigenetic mechanisms play a critical role in the regulation of gene expression as they modify the degree of chromatin compaction to facilitate both activation and repression of transcription. Among the most studied epigenetic mechanisms we find the methylation of DNA, ATP-dependent chromatin remodeling, and enzyme-mediated deposition and elimination of post-translational modifications at histone and non-histone proteins. In this mini review, we discuss evidence that supports the role of these epigenetic mechanisms during transcriptional control of osteoblast-related genes. Special attention is dedicated to mechanisms of epigenetic control operating at the Runx2 and Sp7 genes coding for the two principal master regulators of the osteogenic lineage during mesenchymal stem cell commitment.
在真核细胞核内，基因组DNA通过与组蛋白以及包括非组蛋白和非编码RNA在内的其他几种核成分稳定相互作用，被组织成染色质。这些相互作用共同将遗传物质分布到染色质亚结构域中，这些亚结构域可表现出较高和较低的压缩水平。这种组织有助于差异控制对编码关键调控遗传信息的基因组序列的访问。在这种情况下，表观遗传机制在基因表达调控中起关键作用，因为它们改变染色质压缩程度，以促进转录的激活和抑制。在研究最多的表观遗传机制中，我们发现DNA甲基化、ATP依赖的染色质重塑，以及酶介导的组蛋白和非组蛋白蛋白质翻译后修饰的沉积和消除。在这篇小型综述中，我们讨论了支持这些表观遗传机制在成骨细胞相关基因转录控制中作用的证据。特别关注在间充质干细胞分化过程中，对成骨谱系的两个主要主调控因子Runx2和Sp7基因起作用的表观遗传控制机制。
