Manipulating nuclear architecture

Abstract

The eukaryotic genome is highly organized in the nucleus. Genes can be localized to specific nuclear compartments in a manner reflecting their activity. A plethora of recent reports has described multiple levels of chromosomal folding that can be related to gene-specific expression states. Here we discuss studies designed to probe the causal impact of genome organization on gene expression. The picture that emerges is that of a reciprocal relationship in which nuclear organization is not only shaped by gene expression states but also directly influences them.

Figure 1

Manipulations of gene positioning and looping. (A) Targeting a gene or chromatin domain to the nuclear periphery or other nuclear compartments by DNA-binding protein factors. (B) Forced chromatin looping to produce various outcomes. Juxtaposition of enhancers or silencers with promoters might activate or repress transcription, respectively. Repression might also be achieved by insulating enhancers or inducing competing unproductive loops.