A detailed article by UAB professor Joan-Ramon Daban explores the physical challenges related to DNA packaging, which have frequently been overlooked in chromosome structural models. This research, published in the journal Small Structures, shows that the proposed multilaminar organization of DNA, based on earlier experimental findings from UAB, aligns perfectly with the structural and functional characteristics of chromosomes. The study elucidates that this organization can be attributed to weak interactions between nucleosomes, the repeated units that fold the DNA double helix.
The extremely lengthy genomic DNA found in eukaryotic organisms needs to be tightly packed to fit within the microscopic dimensions of chromosomes during mitosis, safeguarding the genetic information before cell division. Early in evolution, histone proteins evolved to transform DNA into chromatin filaments composed of numerous nucleosomes. Each nucleosome’s core particle is a cylindrical structure measuring 5.7 nanometers in height and 11 nanometers in diameter, which contains approximately two turns of DNA (147 base pairs) wrapped around an octamer of histones. Understanding how chromatin folds into highly compact chromosomes has posed a significant scientific challenge for many years.
A valid and realistic structural model for DNA organization in chromosomes must accommodate all constraints arising from the observed structural and functional characteristics of chromosomes. It should consider the high concentration of DNA, the elongated cylindrical form of chromosomes, the known self-association properties of chromatin, and ensure effective safeguarding of chromosomal DNA against topological entanglement and mechanical breakage. Unfortunately, these important constraints are often overlooked in various models derived from different experimental techniques and computational approaches.
In Professor Joan-Ramon Daban’s lab at UAB’s Department of Biochemistry and Molecular Biology, researchers utilized transmission electron microscopy, atomic force microscopy, and cryo-electron tomography techniques. They found that chromatin derived from chromosomes prepared under ionic metaphase conditions forms planar multilayer structures, where each layer represents a mononucleosome sheet’s thickness. Based on these observations, UAB researchers propose that chromatin filaments in chromosomes fold in a consistent pattern of stacked layers along the chromosome’s axis. This multilayered model adheres to all previously mentioned structural constraints. Moreover, it explains the geometry of chromosome bands and translocations identified in cytogenetic studies, and is compatible with potential physical mechanisms for controlling gene expression and for DNA replication, repair, and distribution to daughter cells.
Chromosomes can be viewed as self-organized liquid crystals
Nucleosomes serve as repetitive building units integrated into the uniform linear structure of double-helical DNA. Various laboratories have demonstrated that isolated nucleosome core particles tend to interact face-to-face, forming sizeable columnar structures. These columnar formations can be attributed to the characteristics of soft-matter systems, where weak anisotropic interactions among nucleosomes and thermal energy facilitate their assembly. Within the multilayer chromosome model, the repetitive weak interactions between nucleosomes lead to the stacking of multiple chromatin layers. These low-energy interactions at the nanoscale account for the self-organization of entire chromosomes, which may be regarded as lamellar liquid crystals, internally interconnected by the covalent backbone of a single DNA molecule.
The natural emergence of distinct three-dimensional patterns parallels recent advancements in nanoscience and nanotechnology, which have seen numerous impressive structures self-assembled from various biological and synthetic building blocks. Professor Daban believes that while molecular biology has unveiled the self-assembly of different biomolecular structures, current research into self-organization of soft-matter systems is largely concentrated in nanotechnology.
The article is featured in the interdisciplinary journal Small Structures, which focuses on microstructures created from nanoparticles, considering perspectives from both nanotechnology and the life sciences.
