Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, Scotland, UK.
Epigenomics. 2012 Feb;4(1):67-80. doi: 10.2217/epi.11.112.
Epigenomic profiling has revealed that substantial portions of genomes in higher eukaryotes are organized into extensive domains of transcriptionally repressive chromatin. The boundaries of repressive chromatin domains can be fixed by DNA elements known as barrier insulators, to both shield neighboring gene expression and to maintain the integrity of chromosomal silencing. Here, we examine the current progress in identifying vertebrate barrier elements and their binding factors. We overview the design of the reporter assays used to define enhancer-blocking and barrier insulators. We look at the mechanisms vertebrate barrier proteins, such as USF1 and VEZF1, employ to counteract Polycomb- and heterochromatin-associated repression. We also undertake a critical analysis of whether CTCF could also act as a barrier protein. There is good evidence that barrier elements in vertebrates can form repressive chromatin domain boundaries. Future studies will determine whether barriers are frequently used to define repressive domain boundaries in vertebrates.
表观基因组分析表明,高等真核生物基因组的大部分都组织成转录抑制性染色质的广泛区域。转录抑制性染色质域的边界可以通过称为屏障绝缘子的 DNA 元件固定,以保护相邻基因的表达并维持染色体沉默的完整性。在这里,我们检查了鉴定脊椎动物屏障元件及其结合因子的最新进展。我们概述了用于定义增强子阻断和屏障绝缘子的报告基因检测的设计。我们研究了脊椎动物屏障蛋白(如 USF1 和 VEZF1)用来对抗 Polycomb 和异染色质相关抑制的机制。我们还对 CTCF 是否也可以作为屏障蛋白进行了批判性分析。有充分的证据表明,脊椎动物中的屏障元件可以形成抑制性染色质域边界。未来的研究将确定在脊椎动物中,屏障是否经常用于定义抑制性域边界。