About this Research Topic
The nuclei of eukaryotic cells are complex structures encapsulating the genome in a small physical space. In spite of initial observations based on light microscopy, describing DNA as an unshaped mass in interphase nuclei, scientists demonstrated that each chromosome is folded in a highly organized fashion and occupies specific territories in the nuclear space. Indeed, chromatin is non-homogenously distributed inside the nucleus, as shown by electron microscopy. In particular, most of the dark chromatin (heterochromatin) is found around the nucleoli or at the nuclear periphery interrupted with euchromatin at nuclear pores. This non–random genome positioning ensures adequate regulation of gene expression and maintenance of genome integrity. Epigenetic mechanisms, acting at different chromatin levels from DNA up to the higher order structures, contribute to the correct folding and positioning of the genome, finely regulating the transcriptional output.
To achieve higher order configurations the genetic material utilizes macroscopic structures of the nucleus, such as the nuclear pores and the nuclear lamina as spatial references. Thus, some epigenetic factors cooperate with nuclear structures to fold and to maintain the steady state of chromatin conformation. Chromatin higher order structures are highly responsive to the environmental changes, which modulate transcriptional expression and cell identity through the action of epigenetic players.
In recent years the study of the epigenome and its role in human disease progression has attracted considerable interest given its potential for developing epigenetic-targeted therapies. Such therapies could profoundly change modern medicine acting beyond the DNA sequence by epigenetically modulating gene products. At the same time, our knowledge on the chromatin is continuously progressing and epigenetic research inspired the development of novel technologies based on next-generation sequencing that revolutionized the field of molecular biology introducing genome wide quantification of biological processes. By the use of these new technologies, perturbations of genome organization at each level have been described in several pathologies. Further studies discovered that alteration of epigenetic factors is critically linked to the onset and progression of a broad range of human diseases. Moreover, misconfigured chromatin can be more susceptible to environmental changes leading to a secondary cascade of genome dysfunctions. Besides the plasticity of the chromatin, fundamental for fine-regulated processes, the nuclear structures and shape can also influence important cellular processes and are hallmarks of the healthy cell. Indeed an increasing number of tissue-specific pathologies in humans and tissue-specific phenotypes in model organisms have been described for mutations in a variety of the nuclear architecture components.
In the next future the study of the nucleus and DNA as a whole will have a major impact on the knowledge of human diseases establishing new parameters to understand inter-individual variability, useful for stratification of patients and for monitoring treatment efficacy. This Research Topic focuses on all aspects of chromatin and nuclear alterations in human diseases, in order to create an up-to-date summary of recent findings on epigenetics in human diseases. We welcome the contribution of Original Research and Reviews articles.
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