Gartenberg Marc R, Smith Jeffrey S
Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854.
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908
Genetics. 2016 Aug;203(4):1563-99. doi: 10.1534/genetics.112.145243.
Transcriptional silencing in Saccharomyces cerevisiae occurs at several genomic sites including the silent mating-type loci, telomeres, and the ribosomal DNA (rDNA) tandem array. Epigenetic silencing at each of these domains is characterized by the absence of nearly all histone modifications, including most prominently the lack of histone H4 lysine 16 acetylation. In all cases, silencing requires Sir2, a highly-conserved NAD(+)-dependent histone deacetylase. At locations other than the rDNA, silencing also requires additional Sir proteins, Sir1, Sir3, and Sir4 that together form a repressive heterochromatin-like structure termed silent chromatin. The mechanisms of silent chromatin establishment, maintenance, and inheritance have been investigated extensively over the last 25 years, and these studies have revealed numerous paradigms for transcriptional repression, chromatin organization, and epigenetic gene regulation. Studies of Sir2-dependent silencing at the rDNA have also contributed to understanding the mechanisms for maintaining the stability of repetitive DNA and regulating replicative cell aging. The goal of this comprehensive review is to distill a wide array of biochemical, molecular genetic, cell biological, and genomics studies down to the "nuts and bolts" of silent chromatin and the processes that yield transcriptional silencing.
酿酒酵母中的转录沉默发生在几个基因组位点，包括沉默交配型位点、端粒和核糖体DNA（rDNA）串联阵列。这些结构域中的每一个的表观遗传沉默的特征是几乎所有组蛋白修饰的缺失，最显著的是缺乏组蛋白H4赖氨酸16乙酰化。在所有情况下，沉默都需要Sir2，一种高度保守的依赖NAD(+)的组蛋白脱乙酰酶。在rDNA以外的位置，沉默还需要其他Sir蛋白，Sir1、Sir3和Sir4，它们共同形成一种称为沉默染色质的抑制性异染色质样结构。在过去25年中，对沉默染色质的建立、维持和遗传机制进行了广泛研究，这些研究揭示了转录抑制、染色质组织和表观遗传基因调控的众多范例。对rDNA处Sir2依赖性沉默的研究也有助于理解维持重复DNA稳定性和调节复制性细胞衰老的机制。这篇综述的目的是将大量的生物化学、分子遗传学、细胞生物学和基因组学研究提炼成沉默染色质的“基本要素”以及产生转录沉默的过程。
