DNA甲基化和基因表达调控:我们健康的守护者

IF 2.1 Q4 CELL BIOLOGY Nucleus (India) Pub Date : 2021-01-01 DOI:10.1007/s13237-021-00367-y
Gaurab Aditya Dhar, Shagnik Saha, Parama Mitra, Ronita Nag Chaudhuri
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引用次数: 47

摘要

高等真核生物基因组中最重要的表观遗传特征之一是胞嘧啶环C-5位置DNA的甲基化。根据基因座上DNA甲基化的位点,它可以作为基因表达的抑制或激活标记。在与组蛋白修饰因子的串扰中,DNA甲基化因此可以抑制转录机制的结合或产生有利于转录的环境。在发育阶段,基因组中的DNA甲基化模式由于新生DNA甲基化和去甲基化之间的调节平衡而发生改变。因此,分化的细胞继承了一种独特的DNA甲基化模式,这种模式可以微调组织特异性基因的表达。DNA甲基化虽然表面上是一个稳定的表观遗传标记,但实际上是不稳定的,是表观基因组、基因组和环境因素在出生前和生命发展过程中相互作用的复杂反映。最近的研究结果表明,个体DNA甲基化水平是一个动态结果,在生殖细胞形成、胚胎发生和出生后暴露期间受到饮食环境的强烈影响。在发育阶段DNA甲基化平衡的丧失可能导致印记障碍,而在任何后期阶段都可能导致各种疾病和异常的易感性增加。这篇综述的目的是概述我们的表观基因组是如何被我们从子宫开始的一生经历所独特引导的,以及如何更好地理解它,以更好地把握未来临时临床应用的可能性。
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DNA methylation and regulation of gene expression: Guardian of our health.

One of the most critical epigenetic signatures present in the genome of higher eukaryotes is the methylation of DNA at the C-5 position of the cytosine ring. Based on the sites of DNA methylation in a locus, it can serve as a repressive or activation mark for gene expression. In a crosstalk with histone modifiers, DNA methylation can consequently either inhibit binding of the transcription machinery or generate a landscape conducive for transcription. During developmental phases, the DNA methylation pattern in the genome undergoes alterations as a result of regulated balance between de novo DNA methylation and demethylation. Resultantly, differentiated cells inherit a unique DNA methylation pattern that fine tunes tissue-specific gene expression. Although apparently a stable epigenetic mark, DNA methylation is actually labile and is a complex reflection of interaction between epigenome, genome and environmental factors prior to birth and during progression of life. Recent findings indicate that levels of DNA methylation in an individual is a dynamic outcome, strongly influenced by the dietary environment during germ cell formation, embryogenesis and post birth exposures. Loss of balances in DNA methylation during developmental stages may result in imprinting disorders, while at any later stage may lead to increased predisposition to various diseases and abnormalities. This review aims to provide an outline of how our epigenome is uniquely guided by our lifetime of experiences beginning in the womb and how understanding it better holds future possibilities of improvised clinical applications.

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来源期刊
Nucleus (India)
Nucleus (India) Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.90
自引率
0.00%
发文量
26
期刊介绍: The journal publishes original, peer-reviewed articles on new and significant advances in all aspects of cell and chromosome research. Timely and substantial articles in the areas of cell biology, genetic toxicology, chromosome evolution, cytogenetics; molecular-, population- and evolutionary genetics; epigenetics; developmental and stress biology; transcriptomics, structural and functional genomics, proteomics, metabolomics, integrated omics and use of tools of bioinformatics in the areas stated herein. Studies demonstrating the use of modern approaches such as genome editing to address technological problems and/or biological questions pertaining to the research areas mentioned above are encouraged. However, the studies should be conducted with appropriate scientific rigor in the design, conduct, validity, and interpretation of results to ensure reliability and reproducibility of the data presented. The papers must be written concisely and be of interest to a broad audience. The journal also publishes comprehensive reviews on current developments and future trends in cell and chromosome research. Such articles should be authoritative, covering all the aspects of a chosen topic, and serve as a resource for students, researchers, and multidisciplinary audience. Authors are welcome to contact the Editor-in-Chief to discuss their topic of interest while preparing a prospective review article. Thematic special issues on cutting edge research in the development of the above stated areas are periodically published by the journal. Articles for such issues are commissioned by the respective topic editor/s.
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