The nuclear periphery is a specialized environment in the nucleus that contributes to genome organization and correspondingly to gene regulation. Mammalian chromosomes and certain genes occupy defined positions within the nucleus that are heritable and tissue specific. Genes located at the nuclear periphery tend to be inactive and this negative regulation can be reversed when they are released from the periphery in certain differentiation systems. Recent work using specially designed systems has shown that genes can be artificially tethered to the nuclear periphery by an affinity mechanism. The next important step will be to identify the endogenous NE (nuclear envelope) and chromatin proteins that participate in affinity-driven NE tethering and determine how they are regulated.

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