Chromatin Condensation May Play Role in Cell Differentiation

Recent research published in Science Advances revealed that, at the nucleosome level, condensed euchromatin behaves like a viscous liquid in living human cells. Before this study, it was believed that euchromatin had an open conformation, allowing large proteins associated with gene transcription access to genomic DNA. However, a team led by Professor Kazuhiro Maeshima of SOKENDAI and the National Institute of Genetics utilized a combination of genomics, single-nucleosome imaging, and computational modeling to assess euchromatin. 

The team identified that it essentially forms condensed domains that behave like a viscous fluid at the nucleosome level and like a solid at the chromosome level.

The researchers introduced fluorescently-labeled nucleotides into living cells and visualized nucleosomes near one another using super-resolution microscopes. In doing so, they observed that the nucleosomes' dynamic, liquid-like behavior allowed active transcription even in condensed euchromatin, which challenges conventional thinking about euchromatin's conformation.

The condensed domains can protect DNA from radiation damage by reducing physical access to DNA and decreasing reactive chemical production.

At the chromosomal level, euchromatin appeared to behave like a solid, which may limit DNA damage by reducing entanglements of long DNA strands. This new understanding of the physical nature of expressed genome regions in human cells provides a mechanism to decrease the “stickiness” of chromatin through the acetylation of histones, which opens up chromatin structure to accommodate large transcription or replication complexes, as well as regulate gene expression.

The research team notes that chromatin condensation and organization may play an important role in cell differentiation, as the chromatin domains of undifferentiated embryonic mouse stem cells are more fluid and less defined.

These new imaging techniques will also provide a way for researchers to investigate other nanometer-scale molecules' intracellular dynamics. The team hopes these findings can help scientists better understand gene regulation, DNA replication, and cellular repair mechanisms.