Functional and mechanistic diversity of distal transcription enhancers.

Functional and mechanistic diversity of distal transcription enhancers.
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DOI:
10.1016/j.cell.2011.01.024
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发表时间:
2011-02-04
期刊:
影响因子:
64.5
通讯作者:
Groudine M
Groudine M
中科院分区:
生物学1区
文献类型:
--
作者:
Bulger M;Groudine M

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后生动物之间以及给定生物体中细胞类型之间的生物学差异在很大程度上是由于基因表达模式的差异而产生的。多个后生动物基因组的测序,加上组蛋白修饰和转录因子结合的全基因组分析的最新进展,揭示了在调控 DNA 序列中,基因远端增强子似乎表现出最大的多样性和细胞类型特异性。此外,这些元素正在成为突变的重要目标,这些突变可能导致疾病和进化变化背后的遗传变异。对细胞核中远端基因组序列之间的长程相互作用的研究表明,增强子通常是核组织的重要决定因素,有助于建立涉及增强子-启动子直接接触的增强子功能的通用模型。然而,在许多系统中,增强子功能的机制正在出现,这些机制不仅仅适合这样的模型,这表明增强子作为一类 DNA 调控元件可能在功能和机制上具有多样性。
Biological differences among metazoans, and between cell types in a given organism, arise in large part due to differences in gene expression patterns. The sequencing of multiple metazoan genomes, coupled with recent advances in genome-wide analysis of histone modifications and transcription factor binding, has revealed that among regulatory DNA sequences, gene-distal enhancers appear to exhibit the greatest diversity and cell-type specificity. Moreover, such elements are emerging as important targets for mutations that can give rise to disease and to genetic variability that underlies evolutionary change. Studies of long-range interactions between distal genomic sequences in the nucleus indicate that enhancers are often important determinants of nuclear organization, contributing to a general model for enhancer function that involves direct enhancer-promoter contact. In a number of systems, however, mechanisms for enhancer function are emerging that do not fit solely within such a model, suggesting that enhancers as a class of DNA regulatory element may be functionally and mechanistically diverse.
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