Abstract
The eukaryotic nucleus controls most cellular processes. It is isolated from the cytoplasm by the nuclear envelope, which plays a prominent role in the structural organization of the cell, including nucleocytoplasmic communication, chromatin positioning, and gene expression. Alterations in nuclear composition and function are eminently pronounced upon stress and during premature and physiological aging. These alterations are often accompanied by epigenetic changes in histone modifications. We review, here, the role of nuclear envelope proteins and histone modifiers in the 3-dimensional organization of the genome and the implications for gene expression. In particular, we focus on the nuclear lamins and the chromatin-associated protein BAF, which are linked to Hutchinson–Gilford and Nestor–Guillermo progeria syndromes, respectively. We also discuss alterations in nuclear organization and the epigenetic landscapes during normal aging and various stress conditions, ranging from yeast to humans.
Highlights
IntroductionAll organisms are constantly exposed to a variety of stressors, including both environmental (such as temperature, pathogens, or nutrient availability) and internal factors (like cellular stress, mutations, or physiological aging)
All organisms are constantly exposed to a variety of stressors, including both environmental and internal factors
We focus on the nuclear lamins and the chromatin-associated protein BAF, which are linked to Hutchinson–Gilford and Nestor–Guillermo progeria syndromes, respectively
Summary
All organisms are constantly exposed to a variety of stressors, including both environmental (such as temperature, pathogens, or nutrient availability) and internal factors (like cellular stress, mutations, or physiological aging). Constitutive heterochromatin contains many repetitive elements, frequent H3K9 methylation, and remains transcriptionally silent, while facultative chromatin is enriched for methylated H3K27 and genes that are only expressed at specific moments, for instance, during development. Heterochromatin typically accumulates at the nuclear periphery, whereas euchromatin is positioned in the nuclear interior Since changes in this distribution are a characteristic of aging and senescence [9], we open our discussion with an overview of the role of the NE as chromatin organizer, followed by a recapitulation of the current knowledge about how mutations in NE genes are responsible for the development of the accelerated aging syndromes.
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