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首页> 外文期刊>Epigenetics & Chromatin >A permissive chromatin structure is adopted prior to site-specific DNA demethylation of developmentally expressed genes involved in macronuclear differentiation
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A permissive chromatin structure is adopted prior to site-specific DNA demethylation of developmentally expressed genes involved in macronuclear differentiation

机译：在涉及大核分化的发育表达基因的位点特异性DNA脱甲基化之前，采用允许的染色质结构

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Background DNA methylation and demethylation are important epigenetic regulatory mechanisms in eukaryotic cells and, so far, only partially understood. We exploit the minimalistic biological ciliate system to understand the crosstalk between DNA modification and chromatin structure. In the macronucleus of these cells, the DNA is fragmented into individual short DNA molecules, each representing a functional expression and replication unit. Therefore, long range epigenomic interaction can be excluded in this system. Results In the stichotrichous ciliate Stylonychia lemnae, cytosine methylation occurs in a small subset of macronuclear nanochromosomes expressed only during sexual reproduction. Methylation pattern shows similarity to that observed in fungi and Drosophila. Cytosine methylation correlates with gene activity and chromatin structure. Upon gene activation, cytosines become demethylated and a redistribution of histone post-translational modifications (PTMs) takes place. Evidence is presented that the formation of a permissive chromatin structure in the vicinity of the 5meCs precedes cytosine methylation and is probably a necessary prerequisite for their demethylation. Shortly after demethylation of cytosines occurs, the parental macronucleus degenerates, a new macronucleus is formed from a micronuclear derivative and the specific methylation pattern is transmitted from the germline micronucleus to the new macronucleus. Conclusions We show that very few, or even only one, discrete methylated cytosines are required to assign regulatory functions at a specific locus. Furthermore, evidence is provided that a permissive chromatin structure is probably a necessary prerequisite for the demethylation of specific cytosines. Our results allow us to propose a mechanistic model for the biological function of cytosine methylation in the ciliate cell and its regulation during the cell cycle.
机译：背景DNA甲基化和去甲基化是真核细胞中重要的表观遗传调控机制，到目前为止，仅部分了解。我们利用简约的生物学纤毛系统来了解DNA修饰与染色质结构之间的串扰。在这些细胞的大核中，DNA片段化成单个短的DNA分子，每个分子代表一个功能性表达和复制单元。因此，在该系统中可以排除远距离的表观基因组相互作用。结果在棘突状纤毛的Stylonychia lemnae中，胞嘧啶甲基化发生在一小部分仅在有性生殖期间表达的大核纳米染色体中。甲基化模式显示与真菌和果蝇中观察到的相似。胞嘧啶甲基化与基因活性和染色质结构相关。基因激活后，胞嘧啶脱甲基，并发生组蛋白翻译后修饰（PTM）的重新分布。证据表明，在5meCs附近形成允许的染色质结构先于胞嘧啶甲基化，这可能是它们脱甲基化的必要先决条件。胞嘧啶脱甲基发生后不久，亲代大细胞核变性，由微核衍生物形成新的大核，并且特定的甲基化模式从种系微核传递至新的大核。结论我们表明，很少或什至只有一个离散的甲基化胞嘧啶在特定基因座上分配调节功能。此外，有证据表明，允许的染色质结构可能是特定胞嘧啶脱甲基化的必要先决条件。我们的结果使我们能够为纤毛细胞胞嘧啶甲基化的生物学功能及其在细胞周期中的调控提供一个机制模型。

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