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Background: The spatial organization of eukaryotic genomes facilitates and reflects the underlying nuclear processes that are occurring in the cell. As such, the spatial organization of a genome represents a window on the genome biology that enables analysis of the nuclear regulatory processes that contribute to mammalian development., Methods: In this study, Hi-C and RNA-seq were used to capture the genome organization and transcriptome in mouse muscle progenitor cells (C2C12 myoblasts) before and after differentiation to myotubes, in the presence or absence of the cytidine analogue AraC., Results: We observed significant local and global developmental changes despite high levels of correlation between the myotubes and myoblast genomes. Notably, the genes that exhibited the greatest variation in transcript levels between the different developmental stages were predominately within the euchromatic compartment. There was significant re-structuring and changes in the expression of replication-dependent histone variants within the HIST1 locus. Finally, treating terminally differentiated myotubes with AraC resulted in additional changes to the transcriptome and 3D genome organization of sets of genes that were all involved in pyroptosis., Conclusions: Collectively, our results provide evidence for muscle cell-specific responses to developmental and environmental stimuli mediated through a chromatin structure mechanism.

Chromosome Conformation Capture techniques regularly detect physical interactions between mitochondrial and nuclear DNA (i.e. mito-nDNA interactions) in mammalian cells. We have evaluated mito-nDNA interactions captured by HiC and Circular Chromosome Conformation Capture (4C). We show that these mito-nDNA interactions are statistically significant and shared between biological and technical replicates. The most frequent interactions occur with repetitive DNA sequences, including centromeres in human cell lines and the 18S rDNA in mouse cortical astrocytes. Our results demonstrate a degree of selective regulation in the identity of the interacting mitochondrial partners confirming that mito-nDNA interactions in mammalian cells are not random., (Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

We can now sequence and identify genome wide epigenetic patterns and perform a variety of "genomic experiments" within relatively short periods of time-ranging from days to weeks. Yet, despite these technological advances, we have a poor understanding of the inter-relationships between epigenetics, genome structure-function, and nutrition. Perhaps this limitation lies, in part, in our propensity to study epigenetics in terms of the linear arrangement of elements and genes. Here we propose that a more complete understanding of how nutrition impacts on epigenetics and cellular development resides within the inter-relationships between DNA and histone modification patterns and genome function, in the context of spatial organization of chromatin and the epigenome.