Department of Biochemistry and Molecular Biology and Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain.
Adv Exp Med Biol. 2017;966:65-92. doi: 10.1007/5584_2017_58.
The organisation of chromatin is first discussed to conclude that nucleosomes play both structural and transcription-regulatory roles. The presence of nucleosomes makes difficult the access of transcriptional factors to their target sequences and the action of RNA polymerases. The histone post-translational modifications and nucleosome remodelling are first discussed, from a historical point of view, as mechanisms to remove the obstacles imposed by chromatin structure to transcription. Instead of reviewing the state of the art of the whole field, this review is centred on some open questions. First, some "non-classical" histone modifications, such as short-chain acylations other than acetylation, are considered to conclude that their relationship with the concentration of metabolic intermediaries might make of them a sensor of the physiological state of the cells. Then attention is paid to the interest of studying chromatin organisation and epigenetic marks at a single nucleosome level as a complement to genome-wide approaches. Finally, as a consequence of the above questions, the review focuses on the presence of multiple histone post-translational modifications on a single nucleosome. The methods to detect them and their meaning, with special emphasis on bivalent marks, are discussed.
首先讨论染色质的组织，得出核小体在结构和转录调控方面都发挥作用的结论。核小体的存在使得转录因子难以接近其靶序列，也影响 RNA 聚合酶的作用。从历史的角度首先讨论了组蛋白的翻译后修饰和核小体重塑，作为去除染色质结构对转录的障碍的机制。本综述的重点不是综述整个领域的最新进展，而是集中在一些悬而未决的问题上。首先，考虑了一些“非经典”的组蛋白修饰，如除乙酰化以外的短链酰化，以得出它们与代谢中间产物浓度的关系可能使它们成为细胞生理状态的传感器的结论。然后，关注在单个核小体水平上研究染色质组织和表观遗传标记的意义，作为全基因组方法的补充。最后，由于上述问题，本综述重点讨论了单个核小体上存在多种组蛋白翻译后修饰。讨论了检测它们的方法及其意义，特别强调了双价标记。
