Department of Biochemistry, Purdue University, West Lafayette, Indiana, United States of America.
Purdue University Center for Cancer Research, West Lafayette, Indiana, United States of America.
PLoS Genet. 2020 Dec 7;16(12):e1009226. doi: 10.1371/journal.pgen.1009226. eCollection 2020 Dec.
Replication-coupled chromatin assembly is achieved by a network of alternate pathways containing different chromatin assembly factors and histone-modifying enzymes that coordinate deposition of nucleosomes at the replication fork. Here we describe the organization of a CAF-1-dependent pathway in Saccharomyces cerevisiae that regulates acetylation of histone H4 K16. We demonstrate factors that function in this CAF-1-dependent pathway are important for preventing establishment of silenced states at inappropriate genomic sites using a crippled HMR locus as a model, while factors specific to other assembly pathways do not. This CAF-1-dependent pathway required the cullin Rtt101p, but was functionally distinct from an alternate pathway involving Rtt101p-dependent ubiquitination of histone H3 and the chromatin assembly factor Rtt106p. A major implication from this work is that cells have the inherent ability to create different chromatin modification patterns during DNA replication via differential processing and deposition of histones by distinct chromatin assembly pathways within the network.
复制偶联的染色质组装是通过一个包含不同染色质组装因子和组蛋白修饰酶的交替途径网络来实现的，这些因子和酶协调在复制叉处核小体的沉积。在这里，我们描述了酿酒酵母中一种依赖 CAF-1 的途径的组织，该途径调节组蛋白 H4 K16 的乙酰化。我们证明，在使用一个受损的 HMR 基因座作为模型的情况下，该途径中的因子对于防止在不适当的基因组位点建立沉默状态非常重要，而其他组装途径特有的因子则不重要。这种依赖 CAF-1 的途径需要 cullin Rtt101p，但与涉及依赖 Rtt101p 的组蛋白 H3 泛素化和染色质组装因子 Rtt106p 的另一种途径在功能上是不同的。这项工作的一个主要意义是，细胞在 DNA 复制过程中通过网络中不同的染色质组装途径对组蛋白进行不同的加工和沉积，从而具有内在的能力来创建不同的染色质修饰模式。
