Rice researchers have discovered the key to chromosome structure

Rice University researchers are making progress in understanding how chromosome structures evolve throughout the cell life cycle. Their study of the motorized processes that actively influence chromosome organization was published in the journal Proceedings of the National Academy of Sciences.

“This research provides a better understanding of how motorized processes shape chromosomal structures and influence cellular functions,” said Pierre Wolynes, co-author of the study and the DR Bullard-Welch Foundation Professor of Science. Wolynes is also a professor of chemistry, biosciences, physics and astronomy and co-director of the Center for Theoretical Biological Physics (CTBP).

The research presents two types of motorized chain models: swimming motors and wrestling motors. These motors play distinct roles in manipulating chromosome structure.

Swimming motors, similar to RNA polymerases (enzymes that copy DNA sequences into RNA), help extend and contract the chromatin fiber during gene decoding. Grappling motors pull distant segments of the chromatin fibers together, creating the long-range correlations needed to keep the chromosome knot free.

Motor proteins, which consume chemical energy, play a critical role in shaping chromosome architecture. The researchers studied how these proteins impact ideal polymer chains. They found that swimming motors can cause contraction or expansion depending on the forces applied. In contrast, grappling motors produce consistent long-range effects, consistent with patterns observed in Hi-C experiments, which identify chromatin interactions in the cell nucleus during interphase, a stage of the cell cycle when a cell is not dividing and chromosomes are decondensed and spread throughout the nucleus. The motors that do this are particularly weak and would easily stop when loops form, so the researchers looked for a way to speed them up.

“This study is notable for its use of theoretical modeling of chromosome chain organization by motor proteins,” said Zhiyu Caoco-author of the study and graduate student at CTBP.

Using a statistical mechanics approach, the researchers created a consistent description that predicts the spatial distribution of loop extrusion probabilities. This model helped understand how the motors’ responses to the forces exerted by randomly flipping DNA can be overcome, so that they can still perform the packaging needed to insert the long chromosome chain into the microscopic cell nucleus.

The three-dimensional organization of chromosomes affects vital biological processes such as DNA replication and cell differentiation as embryos develop.

This study was funded by Rice’s Bullard-Welch Chair (grant C-0016) and the National Science Foundation-sponsored Center for Theoretical Biological Physics (grant PHY-2019745).