Department of Chemistry, Princeton University, Princeton, NJ, USA.
Nat Rev Genet. 2024 Apr;25(4):255-271. doi: 10.1038/s41576-023-00664-z. Epub 2023 Nov 20.
Genetic and genomic techniques have proven incredibly powerful for identifying and studying molecular players implicated in the epigenetic regulation of DNA-templated processes such as transcription. However, achieving a mechanistic understanding of how these molecules interact with chromatin to elicit a functional output is non-trivial, owing to the tremendous complexity of the biochemical networks involved. Advances in protein engineering have enabled the reconstitution of 'designer' chromatin containing customized post-translational modification patterns, which, when used in conjunction with sophisticated biochemical and biophysical methods, allow many mechanistic questions to be addressed. In this Review, we discuss how such tools complement established 'omics' techniques to answer fundamental questions on chromatin regulation, focusing on chromatin mark establishment and protein-chromatin interactions.
遗传和基因组技术已被证明在鉴定和研究涉及 DNA 模板过程（如转录）的表观遗传调控的分子参与者方面非常强大。然而，由于涉及的生化网络极其复杂，要实现这些分子如何与染色质相互作用以产生功能输出的机制理解并非易事。蛋白质工程的进步使包含定制翻译后修饰模式的“设计”染色质的重建成为可能，当与复杂的生化和生物物理方法结合使用时，许多机制问题可以得到解决。在这篇综述中，我们讨论了这些工具如何补充现有的“组学”技术来回答关于染色质调控的基本问题，重点是染色质标记的建立和蛋白质-染色质相互作用。
