Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; email:
Annu Rev Genomics Hum Genet. 2021 Aug 31;22:147-170. doi: 10.1146/annurev-genom-120220-085159. Epub 2021 Mar 29.
Nucleosomes wrap DNA and impede access for the machinery of transcription. The core histones that constitute nucleosomes are subject to a diversity of posttranslational modifications, or marks, that impact the transcription of genes. Their functions have sometimes been difficult to infer because the enzymes that write and read them are complex, multifunctional proteins. Here, we examine the evidence for the functions of marks and argue that the major marks perform a fairly small number of roles in either promoting transcription or preventing it. Acetylations and phosphorylations on the histone core disrupt histone-DNA contacts and/or destabilize nucleosomes to promote transcription. Ubiquitylations stimulate methylations that provide a scaffold for either the formation of silencing complexes or resistance to those complexes, and carry a memory of the transcriptional state. Tail phosphorylations deconstruct silencing complexes in particular contexts. We speculate that these fairly simple roles form the basis of transcriptional regulation by histone marks.
核小体包裹 DNA 并阻碍转录机器的进入。构成核小体的核心组蛋白会受到多种翻译后修饰的影响,这些修饰会影响基因的转录。由于书写和读取这些修饰的酶是复杂的多功能蛋白,因此它们的功能有时难以推断。在这里,我们检查了这些修饰的功能的证据,并认为主要的修饰在促进转录或阻止转录方面只执行相当少量的功能。组蛋白核心上的乙酰化和磷酸化会破坏组蛋白-DNA 接触,或使核小体不稳定,从而促进转录。泛素化会刺激甲基化,为沉默复合物的形成或对这些复合物的抗性提供支架,并携带转录状态的记忆。尾部磷酸化在特定情况下破坏沉默复合物。我们推测,这些相当简单的作用构成了组蛋白修饰转录调控的基础。