The insulation of genes from external enhancers and silencing chromatin

The insulation of genes from external enhancers and silencing chromatin
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DOI:
10.1073/pnas.162342499
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发表时间:
2002-12-10
影响因子:
11.1
通讯作者:
Felsenfeld, G
Felsenfeld, G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Burgess-Beusse, B;Farrell, C;Felsenfeld, G

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绝缘体是DNA序列元件,在某些情况下可以作为屏障保护基因免受邻近无活性浓缩染色质的侵犯。一些绝缘子也可以作为阻断元件,以防止与其他基因相关的远端增强子的激活影响。虽然目前发现的大多数绝缘体来自果蝇,但它们也存在于脊椎动物中。鸡-珠蛋白位点5'端的绝缘体标志着开放染色质结构域和组成性凝聚染色质区域之间的边界。对该元件的详细分析表明,它既具有增强子阻断活性,又具有针对位置效应筛选报告基因的能力。增强子阻断与CTCF蛋白结合有关;结合CTCF的位点在基因组的其他关键点上被发现。对位置效应的保护涉及与组蛋白乙酰化和甲基化控制相关的其他特性。因此,绝缘体是一种复杂的元件,可以帮助保存嵌入基因组的基因的独立功能,在基因组中,它们被它们必须忽略的调控信号所包围。
Insulators are DNA sequence elements that can serve in some cases as barriers to protect a gene against the encroachment of adjacent inactive condensed chromatin. Some insulators also can act as blocking elements to protect against the activating influence of distal enhancers associated with other genes. Although most of the insulators identified so far derive from Drosophila, they also are found in vertebrates. An insulator at the 5' end of the chicken beta-globin locus marks a boundary between an open chromatin domain and a region of constitutively condensed chromatin. Detailed analysis of this element shows that it possesses both enhancer blocking activity and the ability to screen reporter genes against position effects. Enhancer blocking is associated with binding of the protein CTCF; sites that bind CTCF are found at other critical points in the genome. Protection against position effects involves other properties that appear to be associated with control of histone acetylation and methylation. Insulators thus are complex elements that can help to preserve the independent function of genes embedded in a genome in which they are surrounded by regulatory signals they must ignore.