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. 2017 Feb 1;28(3):364-369.
doi: 10.1091/mbc.E16-03-0149.

Genetic and epigenetic control of the spatial organization of the genome

Jason Brickner  1
Affiliations

Genetic and epigenetic control of the spatial organization of the genome

Jason Brickner. Mol Biol Cell. .

Abstract

Eukaryotic genomes are spatially organized within the nucleus by chromosome folding, interchromosomal contacts, and interaction with nuclear structures. This spatial organization is observed in diverse organisms and both reflects and contributes to gene expression and differentiation. This leads to the notion that the arrangement of the genome within the nucleus has been shaped and conserved through evolutionary processes and likely plays an adaptive function. Both DNA-binding proteins and changes in chromatin structure influence the positioning of genes and larger domains within the nucleus. This suggests that the spatial organization of the genome can be genetically encoded by binding sites for DNA-binding proteins and can also involve changes in chromatin structure, potentially through nongenetic mechanisms. Here I briefly discuss the results that support these ideas and their implications for how genomes encode spatial organization.

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Figures

FIGURE 1:
FIGURE 1:
Phenomena that lead to nonrandom spatial arrangement of the genome. (A) During development, genes that are induced often move from a peripheral position in association with the lamina, where they are silenced, to a more internal site, where they are expressed (green locus). (B) Gene activation can lead to looping of genes out of their respective chromosome territories, where they can cluster together. (C) Upon activation (green locus), certain genes physically associate with the NPC, causing them to localize to the nuclear periphery. Thus the nuclear periphery is associated with both silencing (red locus at the lamina) and activation/poising (at the NPC). (D) Genes that are targeted to the NPC in budding yeast frequently undergo interallelic clustering and interchromosomal clustering with other genes that are targeted by the same mechanism.
FIGURE 2:
FIGURE 2:
Transcription factors and chromatin function to control interactions with the nuclear periphery. (A) Targeting of genes to the nuclear lamina requires both transcription factors such as c-Krox and YY1 and methylation of histone H3 on lysine 9 (red circles). In C. elegans, this involves a nuclear envelope–localized protein called CEC-4 that binds to this mark. (B) Targeting to the NPC (or interaction with nuclear pore proteins in the nucleoplasm of Drosophila or mammals) requires transcription factors and, in some cases, chromatin changes. Several yeast transcription factors are both necessary and sufficient to cause targeting to the NPC. However, histone acetylation, H3K4 methylation (green circles), and H2A.Z incorporation (green nucleosomes) are also required in certain cases.
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