Cryo-imaging reveals how cells efficiently store the genome
Our cells use an ensemble of histone proteins to fold and package the DNA genome into the nucleus. Histones also determine whether to expose DNA to enzymes to allow processes like gene expression, replication, and repair to occur. Although many in vitro studies have explored the mechanism histones use to fold and package DNA into higher-order structures called chromatin, less is known about chromatin organisation inside the nucleus of intact cells, and understanding this phenomenon could be key to understanding multiple DNA-associated processes. Recent advances in cryo-electron tomography have enabled scientists to observe these structures within the nucleus of rapidly cryopreserved cells. Reporting in Nature Communications, scientists at the University of Oxford collaborated with the electron Bio-Imaging Centre (eBIC) at the Diamond Light Source to capture chromatin in the nucleus of immune T cells, revealing that DNA is folded into more flexible and heterogenous fibres than previously modelled. Their experiments lay the groundwork for future studies into the roles of chromatin in health and disease.
Packing the essentials
Have you ever rushed to pack clothes into a suitcase and skipped the folding step only to find the suitcase wouldn’t close? Though it may have been a struggle, it doesn’t compare to the challenge our cells face when they pack 2 metres of DNA into a nucleus 200,000 times smaller in width. Here an efficient folding mechanism is key, and histone proteins direct the operation.
A complex of histone proteins act as a spool around which 147 base pairs of DNA can wind like thread. Multiple histone spools called nucleosomes can be found along the length of a DNA molecule and coil its strands into so-called chromatin. When chromatin is purified and observed using electron microscopy, scientists have observed that nucleosomes are spaced apart at regular intervals like beads on a string. These beads can then cluster together to form thicker chromatin fibres that pack the DNA into an even smaller volume.
Beyond efficiently folding DNA to fit inside the nucleus, histones play vital roles in regulating gene expression, DNA replication, and repair by loosening or tightening their grip on DNA and controlling its exposure to enzymes. An in-depth understanding of the folding mechanism could help researchers understand how chromatin affects multiple processes within the nucleus.
Read more on the Diamond website