Research Topic

How does nuclear structure control genome function throughout the life-span and then fail in disease?

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Maintaining a healthy genome is paramount to living a long disease-free life. Our genomes exist within, are protected by and controlled through the complex environment of the cell nucleus. The cell nucleus has many structural components which have intimate regulatory relationships with our chromosomes and ...

Maintaining a healthy genome is paramount to living a long disease-free life. Our genomes exist within, are protected by and controlled through the complex environment of the cell nucleus. The cell nucleus has many structural components which have intimate regulatory relationships with our chromosomes and genes, allowing them to replicate, modify their chromatin and produce gene products. Many structures not only anchor genomic regions, bringing about a strict spatial organization within nuclei, but translate signals to the chromatin in order to elicit a response through gene regulation or chromatin modification. These structures include nucleoli, numerous nuclear bodies, “the nucleoskeleton”, the nuclear envelope and nuclear pores within the nuclear envelope. In order to give a complete picture of nuclear function and influence over the genome we will include articles on all these structures but with more of a focus on the nuclear envelope due to its involvement in nuclear reassembly, genome organization and chromosome and gene positioning and ageing. Furthermore many studies have found that the nuclear envelope in cancer cells is affected in shape and composition and this now being linked to diagnostic and prognostic outputs. Furthermore, many expert cell biologists are using a plethora of approaches to determine how the nuclear envelope (nuclear membrane, associated proteins and the nuclear lamina) interacts and influences the genome; due to a number of degenerative diseases in various tissues of the mesenchyme as well as neuronal cells being caused by mutations in nuclear lamin proteins and their binding partners. Mutations in the lamin A gene have also been shown to be responsible for premature ageing syndromes such as Hutchinson Gilford Progeria Syndrome. These cells contain a truncated toxic form of lamin A that is also found in normal aged cells; implying that the health of the nuclear envelope is critical in ageing well.
The nucleolus can be an overlooked sub-organelle in cells with respect to influence over genome function but it is clear to us (and the people we would welcome to discuss this in their articles) that the nucleoli will be found to play a critical role in controlling genome organization, chromatin modification and gene expression in health, ageing and disease. Another hypothetical point of discussion in this Research Topic will be the articles presented on the role of nuclear bodies and their actual and hypothetical roles in eliciting gene expression and processing of transcripts. Many of these bodies are missing or mislocalised in disease which could impact on their genome interactions.
Thus, we have included a list of potential contributors covering spatial and temporal control of the mechanisms of the genome through nuclear structure, technologies for studying the nucleus in health and disease from embryonic cells to aged cells.


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