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Trends Genet. 2015 Sep;31(9):483-90. doi: 10.1016/j.tig.2015.07.001. Epub 2015 Aug 7.

Why the activity of a gene depends on its neighbors.

Author information

1
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
2
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address: peter.cook@path.ox.ac.uk.

Abstract

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.

KEYWORDS:

boundary; domain; enhancer; expression quantitative trait loci; position effect; silencer

PMID:
26259670
DOI:
10.1016/j.tig.2015.07.001
[Indexed for MEDLINE]

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