Braunstein M, Rose A B, Holmes S G, Allis C D, Broach J R
Department of Molecular Biology, Princeton University, New Jersey 08544.
Genes Dev. 1993 Apr;7(4):592-604. doi: 10.1101/gad.7.4.592.
Two classes of sequences in the yeast Saccharomyces cerevisiae are subject to transcriptional silencing: the silent mating-type cassettes and telomeres. In this report we demonstrate that the silencing of these regions is strictly associated with acetylation of the epsilon-amino groups of lysines in the amino-terminal domains of three of the four core histones. Both the silent mating-type cassettes and the Y domains of telomeres are packaged in nucleosomes in vivo that are hypoacetylated relative to those packaging active genes. This difference in acetylation is eliminated by genetic inactivation of silencing: The silent cassettes from sir2, sir3, or sir4 cells show the same level of acetylation as other active genes. The correspondence of silencing and hypoacetylation of the mating-type cassettes is observed even for an allele lacking a promoter, indicating that silencing per se, rather than the absence of transcription, is correlated with hypoacetylation. Finally, overexpression of Sir2p, a protein required for transcriptional silencing in yeast, yields substantial histone deacetylation in vivo. These studies fortify the hypothesis that silencing in yeast results from heterochromatin formation and argue that the silencing proteins participate in this formation.
沉默的交配型基因座和端粒。在本报告中，我们证明这些区域的沉默与四种核心组蛋白中三种的氨基末端结构域中赖氨酸的ε-氨基乙酰化密切相关。沉默的交配型基因座和端粒的Y结构域在体内都被包装在核小体中，相对于包装活性基因的核小体，它们的乙酰化程度较低。通过沉默的基因失活消除了这种乙酰化差异：来自sir2、sir3或sir4细胞的沉默基因座显示出与其他活性基因相同的乙酰化水平。即使对于缺乏启动子的等位基因，也观察到交配型基因座的沉默与低乙酰化之间的对应关系，这表明沉默本身而非转录缺失与低乙酰化相关。最后，酵母转录沉默所需的蛋白质Sir2p的过表达在体内产生了大量的组蛋白去乙酰化。这些研究强化了酵母中的沉默是由异染色质形成导致的这一假说，并表明沉默蛋白参与了这种形成。
