Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
Trends Genet. 2011 Oct;27(10):389-96. doi: 10.1016/j.tig.2011.06.006. Epub 2011 Jul 20.
Histone modifications are key components of chromatin packaging but whether they constitute a 'code' has been contested. We believe that the central issue is causality: are histone modifications responsible for differences between chromatin states, or are differences in modifications mostly consequences of dynamic processes, such as transcription and nucleosome remodeling? We find that inferences of causality are often based on correlation and that patterns of some key histone modifications are more easily explained as consequences of nucleosome disruption in the presence of histone modifying enzymes. We suggest that the 35-year-old DNA accessibility paradigm provides a mechanistically sound basis for understanding the role of nucleosomes in gene regulation and epigenetic inheritance. Based on this view, histone modifications and variants contribute to diversification of a chromatin landscape shaped by dynamic processes that are driven primarily by transcription and nucleosome remodeling.
组蛋白修饰是染色质包装的关键组成部分，但它们是否构成“密码”一直存在争议。我们认为核心问题是因果关系：组蛋白修饰是否导致了染色质状态的差异，还是修饰的差异主要是转录和核小体重塑等动态过程的结果？我们发现，因果关系的推断往往基于相关性，而且一些关键组蛋白修饰的模式更容易被解释为组蛋白修饰酶存在时核小体破坏的结果。我们认为，35 年前提出的 DNA 可及性范例为理解核小体在基因调控和表观遗传遗传中的作用提供了一个合理的机制基础。基于这一观点，组蛋白修饰和变体有助于由主要由转录和核小体重塑驱动的动态过程所塑造的染色质景观的多样化。
