Bi X, Braunstein M, Shei G J, Broach J R
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11934-9. doi: 10.1073/pnas.96.21.11934.
The eukaryotic genome is divided into functional domains defined in part by local differences in chromatin structure and delimited in many cases by boundary elements. The HML and HMR loci in the yeast Saccharomyces cerevisiae are transcriptionally silent chromosome domains. Each locus is bracketed by two cis-acting sequences, designated E and I, that serve to establish and maintain repression of genes within each locus. We show that repression at HML is uniformly high between E and I but decreases sharply beyond I. The region of repression at HML generally correlates with the domain of histone hypoacetylation. Despite the sharp definition of the boundaries of HML, no sequence capable of blocking the spread of heterochromatin resides in the sequences flanking HML. We find, though, that inverting the orientation of I increases silencing outside of HML while weakening silencing within HML. These results indicate that the HML I silencer establishes a boundary between active and inactive chromatin at HML, but does so by organizing inactive chromatin in only one direction. This represents a different mechanism for delimiting the boundaries of a eukaryotic chromosome domain.
真核生物基因组被划分为功能结构域，这些结构域部分由染色质结构的局部差异定义，并且在许多情况下由边界元件界定。酿酒酵母中的HML和HMR基因座是转录沉默的染色体结构域。每个基因座由两个顺式作用序列包围，分别称为E和I，它们用于建立和维持每个基因座内基因的抑制作用。我们发现，HML处的抑制作用在E和I之间始终很高，但在I之外急剧下降。HML处的抑制区域通常与组蛋白低乙酰化区域相关。尽管HML的边界定义明确，但在HML侧翼序列中不存在能够阻止异染色质扩散的序列。不过，我们发现，将I的方向颠倒会增强HML外部的沉默作用，同时减弱HML内部的沉默作用。这些结果表明，HML I沉默子在HML处的活性和非活性染色质之间建立了一个边界，但它仅通过在一个方向上组织非活性染色质来实现这一点。这代表了一种界定真核生物染色体结构域边界的不同机制。
