Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Trends Genet. 2015 Sep;31(9):483-90. doi: 10.1016/j.tig.2015.07.001. Epub 2015 Aug 7.
Sixty years ago, the position of a gene on a chromosome was seen to be a major determinant of gene activity; however, position effects are rarely central to current discussions of gene expression. We describe a comprehensive and simplifying view of how position in 1D sequence and 3D nuclear space underlies expression. We suggest that apparently-different regulatory motifs including enhancers, silencers, insulators, barriers, and boundaries act similarly - they are active promoters that tether target genes close to, or distant from, appropriate transcription sites or 'factories'. We also suggest that any active transcription unit regulates the firing of its neighbors - and thus can be categorized as one or other type of motif; this is consistent with expression quantitative trait loci (eQTLs) being widely dispersed.
六十年前,人们认为基因在染色体上的位置是基因活性的主要决定因素;然而,位置效应在当前的基因表达讨论中很少成为核心。我们描述了一个全面而简化的观点,即 1D 序列和 3D 核空间中的位置如何构成表达的基础。我们认为,表观上不同的调节基序,包括增强子、沉默子、绝缘子、屏障和边界,它们的作用类似——它们是活性启动子,将靶基因固定在适当的转录位点或“工厂”附近或远处。我们还表明,任何活跃的转录单元都可以调节其邻近基因的转录——因此可以归类为一种或另一种类型的基序;这与表达数量性状基因座 (eQTL) 广泛分散的情况一致。