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从基因组到表观基因组:在决定个体发育潜在表观遗传机制的分子特征中,谁是主要参与者?

From genome to epigenome: Who is a predominant player in the molecular hallmarks determining epigenetic mechanisms underlying ontogenesis?

作者信息

Samiec Marcin, Trzcińska Monika

机构信息

Department of Reproductive Biotechnology and Cryoconservation, National Research Institute of Animal Production, Krakowska 1 Street, 32-083 Balice near Kraków, Poland.

出版信息

Reprod Biol. 2024 Dec;24(4):100965. doi: 10.1016/j.repbio.2024.100965. Epub 2024 Oct 28.

Abstract

Genetic factors are one of the basic determinants affecting ontogenesis in mammals. Nevertheless, on the one hand, epigenetic factors have been found to exert the preponderant and insightful impact on the intracellular mechanistic networks related to not only initiation and suppression, but also up- and downregulation of gene expression in all the phases of ontogenetic development in a variety of mammalian species. On the other hand, impairments in the epigenetic mechanisms underlying reprogramming of transcriptional activity of genes (termed epimutations) not only give rise to a broad spectrum of acute and chronic developmental abnormalities in mammalian embryos, foetuses and neonates, but also contribute to premature/expedited senescence or neoplastic transformation of cells and even neurodegenerative and mental disorders. The current article is focused on the unveiling the present knowledge aimed at the identification, classification and characterization of epigenetic agents as well as multifaceted interpretation of current and coming trends targeted at recognizing the epigenetic background of proper ontogenesis in mammals. Moreover, the next objective of this paper is to unravel the mechanistic insights into a wide array of disturbances leading to molecular imbalance taking place during epigenetic reprogramming of genomic DNA. The above-indicated imbalance seems to play a predominant role in the initiation and progression of anatomo-, histo-, and physiopathological processes throughout ontogenetic development. Conclusively, different modalities of epigenetically assisted therapeutic procedures that have been exemplified in the current article, might be the powerful and promiseful tools reliable and feasible in the medical treatments of several diseases triggered by dysfunctions in the epigenetic landscapes, e.g., myelodysplastic syndromes or epilepsy.

摘要

遗传因素是影响哺乳动物个体发育的基本决定因素之一。然而,一方面,人们发现表观遗传因素不仅在多种哺乳动物物种个体发育的所有阶段对与基因表达的启动、抑制以及上调和下调相关的细胞内机制网络产生主要且有深刻影响,而且在基因转录活性重编程(称为表观突变)的表观遗传机制中,损伤不仅会在哺乳动物胚胎、胎儿和新生儿中引发广泛的急性和慢性发育异常,还会导致细胞过早/加速衰老或肿瘤转化,甚至引发神经退行性和精神障碍。本文重点在于揭示当前关于表观遗传因子的识别、分类和表征的知识,以及对当前和未来趋势的多方面解读,旨在认识哺乳动物正常个体发育的表观遗传背景。此外,本文的下一个目标是揭示对在基因组DNA表观遗传重编程过程中导致分子失衡的一系列干扰的机制性见解。上述失衡似乎在整个个体发育过程中的解剖、组织和生理病理过程的启动和进展中起主要作用。总之,本文所举例的不同表观遗传辅助治疗程序模式,可能是在治疗由表观遗传景观功能障碍引发的几种疾病(如骨髓增生异常综合征或癫痫)时可靠且可行的强大且有前景的工具。

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