How genetic material is compacted and de-compacted during the different phases of the cell cycle, has been uncovered by researchers at The Wistar Institute. Their study was published in Nature Structural & Molecular Biology yesterday.
"We are just starting to appreciate that the way our genome is spatially organized in our cells has a profound impact on its function," said lead author of the study Ken-ichi Noma, Ph.D., associate professor in the gene expression and regulation program at Wistar. "Deciphering the three-dimensional structure of chromatin is essential to understanding key functions like transcription, DNA replication, and repair."
The Noma lab has extensively studied the mechanisms of genome organization using fission yeast as a model organism because it shares some important features with human cells while having a much smaller genome.
Noma and colleagues have previously described how condensin and cohesin mediate the formation of functional genome-organizing structures called topological domains by establishing contacts that bring distantly located DNA regions closer together. Specifically, cohesin mediates local contacts, forming small topological chromatin domains, whereas condensin drives longer-range contacts, organizing larger domains.
In the new study, the lab applied similar genomic methodology to dissect the condensation and de-condensation of chromatin in topological domains over time, following the formation and decay of chromatin contacts throughout the different phases of the cell cycle. They discovered that the larger domains mediated by condensin are formed during mitosis, whereas the smaller, local domains mediated by cohesin remain stable throughout the whole cycle.
"Contrary to what was generally assumed in the field, we find that condensation and de-condensation of the chromatin domains happen very gradually and the cells oscillate smoothly between more and less condensed chromatin states," said first author of the study Hideki Tanizawa, Ph.D., an associate staff scientist in the Noma lab.
Alterations of the three-dimensional structures of the genome are linked to genetic diseases and cancer, presenting a powerful example of how basic cellular processes are relevant for disease. "The field is still in an early discovery phase but our study adds new insight into a fundamental biological process that may assist the development of novel therapeutic strategies in the future," added Noma.