Department of Genetics & Biotechnology, Saint-Petersburg State University, Saint-Petersburg 199034, Russia.
Biol Rev Camb Philos Soc. 2018 Nov;93(4):1987-2005. doi: 10.1111/brv.12429. Epub 2018 May 22.
Although epigenetic inheritance (EI) is a rapidly growing field of modern biology, it still has no clear place in fundamental genetic concepts which are traditionally based on the hereditary role of DNA. Moreover, not all mechanisms of EI attract the same attention, with most studies focused on DNA methylation, histone modification, RNA interference and amyloid prionization, but relatively few considering other mechanisms such as stable inhibition of plastid translation. Herein, we discuss all known and some hypothetical mechanisms that can underlie the stable inheritance of phenotypically distinct hereditary factors that lack differences in DNA sequence. These mechanisms include (i) regulation of transcription by DNA methylation, histone modifications, and transcription factors, (ii) RNA splicing, (iii) RNA-mediated post-transcriptional silencing, (iv) organellar translation, (v) protein processing by truncation, (vi) post-translational chemical modifications, (vii) protein folding, and (viii) homologous and non-homologous protein interactions. The breadth of this list suggests that any or almost any regulatory mechanism that participates in gene expression or gene-product functioning, under certain circumstances, may produce EI. Although the modes of EI are highly variable, in many epigenetic systems, stable allelic variants can be distinguished. Irrespective of their nature, all such alleles have an underlying similarity: each is a bimodular hereditary unit, whose features depend on (i) a certain epigenetic mark (epigenetic determinant) in the DNA sequence or its product, and (ii) the DNA sequence itself (DNA determinant; if this is absent, the epigenetic allele fails to perpetuate). Thus, stable allelic epigenetic inheritance (SAEI) does not contradict the hereditary role of DNA, but involves additional molecular mechanisms with no or almost no limitations to their variety.
尽管表观遗传遗传（EI）是现代生物学中一个快速发展的领域，但它在传统上基于 DNA 遗传作用的基础遗传概念中仍然没有明确的地位。此外，并非所有的 EI 机制都受到同样的关注，大多数研究集中在 DNA 甲基化、组蛋白修饰、RNA 干扰和淀粉样蛋白朊病毒化，但相对较少考虑其他机制，如稳定抑制质体翻译。在此，我们讨论了所有已知的和一些假设的机制，这些机制可以作为缺乏 DNA 序列差异的表型不同遗传因子稳定遗传的基础。这些机制包括：（i）DNA 甲基化、组蛋白修饰和转录因子对转录的调控；（ii）RNA 剪接；（iii）RNA 介导的转录后沉默；（iv）细胞器翻译；（v）通过截断进行蛋白质加工；（vi）翻译后化学修饰；（vii）蛋白质折叠；（viii）同源和非同源蛋白质相互作用。该列表的广泛范围表明，任何或几乎任何参与基因表达或基因产物功能的调控机制，在某些情况下，都可能产生 EI。尽管 EI 的模式高度多样化，但在许多表观遗传系统中，可以区分稳定的等位基因变体。无论其性质如何，所有这些等位基因都有一个潜在的相似性：每个等位基因都是一个双模块遗传单元，其特征取决于（i）DNA 序列或其产物中的特定表观遗传标记（表观遗传决定因素），以及（ii）DNA 序列本身（DNA 决定因素；如果不存在，表观遗传等位基因就无法延续）。因此，稳定的等位基因表观遗传遗传（SAEI）并不违背 DNA 的遗传作用，而是涉及到额外的分子机制，其多样性几乎没有限制。
