Mihaly J, Hogga I, Barges S, Galloni M, Mishra R K, Hagstrom K, Müller M, Schedl P, Sipos L, Gausz J, Gyurkovics H, Karch F
Department of Zoology and Animal Biology, University of Geneva, Switzerland.
Cell Mol Life Sci. 1998 Jan;54(1):60-70. doi: 10.1007/s000180050125.
Eukaryotic chromosomes are thought to be organized into a series of discrete higher-order chromatin domains. This organization is believed to be important not only in the compaction of the chromatin fibre, but also in the utilization of genetic information. Critical to this model are the domain boundaries that delimit and segregate the chromosomes into units of independent gene activity. In Drosophila, such domain boundaries have been identified through two different approaches. On the one hand, elements like scs/scs' and the reiterated binding site for the SU(HW) protein have been characterized through their activity of impeding enhancer-promoter interactions when intercalated between them. Their role of chromatin insulators can protect transgenes from genomic position effects, thereby establishing independent functional domains within the chromosome. On the other hand, domain boundaries of the Bithorax complex (BX-C) like Fab-7 and Mcp have been identified through mutational analysis. Mcp and Fab-7, however, may represent a specific class of boundary elements; instead of separating adjacent domains that contain separate structural genes. Mcp and Fab-7 delimit adjacent cis-regulatory domains, each of which interacts independently with their target promoters. In this article, we review the genetic and molecular characteristics of the domain boundaries of the BX-C. We describe how Fab-7 functions to confine activating as well as repressive signals to the flanking regulatory domains. Although the mechanisms by which Fab-7 works as a domain boundary remain an open issue, we provide preliminary evidence that Fab-7 is not a mere insulator like scs or the reiterated binding site for the SU(HW) protein.
真核生物染色体被认为是由一系列离散的高阶染色质结构域组成。这种组织结构不仅被认为在染色质纤维的压缩中很重要,而且在遗传信息的利用中也很重要。该模型的关键是域边界,它界定并将染色体分隔成独立基因活动的单元。在果蝇中,通过两种不同的方法已经鉴定出了这样的域边界。一方面,像scs/scs' 这样的元件以及SU(HW) 蛋白的重复结合位点,通过它们插入其间时阻碍增强子-启动子相互作用的活性而被表征。它们作为染色质绝缘子的作用可以保护转基因免受基因组位置效应的影响,从而在染色体内建立独立的功能域。另一方面,通过突变分析已经鉴定出了双胸复合体(BX-C)的域边界,如Fab-7和Mcp。然而,Mcp和Fab-7可能代表了一类特定的边界元件;它们不是分隔包含独立结构基因的相邻结构域,而是界定相邻的顺式调控结构域,每个顺式调控结构域都独立地与其靶启动子相互作用。在本文中,我们综述了BX-C域边界的遗传和分子特征。我们描述了Fab-7如何发挥作用,将激活信号和抑制信号限制在侧翼调控结构域内。尽管Fab-7作为域边界发挥作用的机制仍然是一个悬而未决的问题,但我们提供了初步证据表明Fab-7不像scs或SU(HW) 蛋白的重复结合位点那样仅仅是一个绝缘子。