Remote control of gene transcription

被引:229
作者
West, AG [1 ]
Fraser, P
机构
[1] Univ Glasgow, Western Infirm, Div Canc Sci & Mol Pathol, Glasgow G11 6NT, Lanark, Scotland
[2] Babraham Inst, Lab Chromatin & Gene Express, Cambridge CB2 4AT, England
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
D O I
10.1093/hmg/ddi104
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In this review, we look at the most recent studies of DNA elements that function over long genomic distances to regulate gene transcription and will discuss the mechanisms genes employ to overcome the positive and negative influences of their genomic neighbourhood in order to achieve accurate programmes of expression. Enhancer elements activate high levels of transcription of linked genes from distal locations. Recent technological advances have demonstrated chromatin loop interactions between enhancers and their target promoters. Moreover, there is increasing evidence that these dynamic interactions regulate the repositioning of genes to foci of active transcription within the nucleus. Enhancers have the potential to activate a number of neighbouring genes over a large chromosomal region, hence, their action must be restricted in order to prevent activation of non-target genes. This is achieved by specialized DNA sequences, termed enhancer blockers (or insulators), that interfere with an enhancer's ability to communicate with a target promoter when positioned between the two. Here, we summarize current models of enhancer blocking activity and discuss recent findings of how it can be dynamically regulated. It has become clear that enhancer blocking elements should not be considered only as structural elements on the periphery of gene loci, but as regulatory elements that are crucial to the outcome of gene expression. The transcription potential of a gene can also be susceptible to heterochromatic silencing originating from its chromatin environment. Insulator elements can act as barriers to the spread of heterochromatin. We discuss recent evidence supporting a number of non-exclusive mechanisms of barrier action, which mostly describe the modulation of chromatin structure or modification.
引用
收藏
页码:R101 / R111
页数:11
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