Nuclear neighborhoods and gene expression

Abstract

The eukaryotic nucleus is a highly compartmentalized and dynamic environment. Chromosome territories are arranged nonrandomly within the nucleus and numerous studies have indicated that a gene's position in the nucleus can impact its transcriptional activity. Here, we focus on recent advances in our understanding of the influence of specific nuclear neighborhoods on gene expression or repression. Nuclear neighborhoods associated with transcriptional repression include the inner nuclear membrane/nuclear lamina and perinucleolar chromatin, whereas neighborhoods surrounding the nuclear pore complex, PML nuclear bodies, and nuclear speckles seem to be transcriptionally permissive. While nuclear position appears to play an important role in gene expression, it is likely to be only one piece of a flexible puzzle that incorporates numerous parameters. We are still at a very early, yet exciting stage in our journey toward deciphering the mechanism(s) that govern(s) the permissiveness of gene expression/repression within different nuclear neighborhoods.

Figure 1. Nuclear Neighborhoods

A cartoon of the mammalian cell nucleus showing some of the numerous nuclear domains, or neighborhoods, that have been identified. Several nuclear neighborhoods that have been implicated in gene activation or repression are discussed in the text.

Figure 2. The Impact of Nuclear Neighborhoods on Gene Expression

(A) Protein factors (green) that are enriched in a particular nuclear neighborhood could diffuse to nearby gene loci, thereby negatively (or positively) affecting the expression of genes. (B) The association of a particular gene locus with a nuclear neighborhood may be a consequence of gene activation (or repression), rather than its cause. For example, a gene could be bound and activated by a transcription factor (yellow). Subsequently, a nuclear body may form de novo at the site where the transcription factor is already bound. Alternatively, DNA bound by a protein constituent of a nuclear body (yellow) may dynamically relocate to an already existing nuclear body. (C) Nuclear neighborhood associated proteins (red), may indirectly affect transcription in combination with other protein factors (blue) by stabilizing inter-/intra-chromosomal interactions, or by shielding associated genes from the effect of nearby heterochromatin.