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The three-dimensional organization of DNA in the nucleus influences our biology, from how our genome organized our cellular activity to how genes are passed from parents to children.
X-rays and microscopy showed that the primary level of chromatin organization involves 147 bases of DNA spooling around proteins to form particles approximately 11 nanometers (nm) in diameter called nucleosomes.
These nucleosome “beads on a string” are then thought to fold into discrete fibers of increasing diameter (30, 120, 320 nm etc.), until they form chromosomes.
Researchers used ChromEMT to image and measure chromatin in resting human cells and during cell division (mitosis) when DNA is compacted into its most dense form -the 23 pairs of mitotic chromosomes that are the iconic image of the human genome.
Chromatin that has been extracted from the nucleus and subjected to processing in vitro – in test tubes – may not look like chromatin in an intact cell, so it is tremendously important to be able to see it in vivo.
Chromatin’s packing density, and not some higher-order structure, that determines which areas of the genome are active and which are suppressed.
Controlling access to chromatin could be a useful approach to preventing, diagnosing and treating diseases like cancer.
Chromatin does not need to form discrete higher-order structures to fit in the nucleus, It’s the packing density that could change and limit the accessibility of chromatin, providing a local and global structural basis through which different combinations of DNA sequences, nucleosome variations and modifications could be integrated in the nucleus to exquisitely fine-tune the functional activity and accessibility of our genomes.
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