New York University chemists have employed a computer simulation whose results have enhanced scientific understanding of the packaging of DNA in the cell with applications to DNA transcription. The study, funded by the National Institutes of Health, appeared in the June 7 issue of the Proceedings of the National Academy of Sciences.
New York University chemists have employed a computer simulation whose results have enhanced scientific understanding of the packaging of DNA in the cell with applications to DNA transcription. The study, funded by the National Institutes of Health, appeared in the June 7 issue of the Proceedings of the National Academy of Sciences.
Previous research has indicated that chromatin the substance of chromosomes consisting of proteins and DNAexhibits salt-dependent conformations. Specifically, chains of nucleosomes, the building blocks of chromatin that appear as bead-like structures along DNA, fold into a condensed fiber as salt increases. This folding and the interplay between chromatin structures regulate fundamental gene expression. However, the molecular mechanism underlying this process remains unclear.
The research team, which included NYU’s Tamar Schlick, a chemist, mathematician, and computational biologist, and chemists Jian Sun (now at the Cornell Medical School) and Qing Zhang, analyzed a 12-nucleosome array. Using a variety of salt conditions, the researchers found that the nucleosomal array formed irregular three-dimensional zig-zag structures at high salt concentrations and “beads-on-a-string” structures at low salt, demonstrating how the structure of chromatin strongly depends on its salt environment. Previous research had shown the effect of salt on chromatin conformation, but not how it influenced its molecular make-up.
To Schlick and her colleagues, these results and further energetic analysis revealed that in a low-salt environment, linker DNAs in the array were repelled, preventing array folding and resulting in a bead-like structure. However, under high-salt conditions, screening of linker DNA repulsion allows close contacts and attraction between nucleosomes, allowing the array to fold. As chromatin folding or unfolding prevents or allows the transcriptional machinery’s access to the DNA in a chromosome, this computer simulation study helps biologists understand in molecular detail the process of chromatin folding and unfolding, and thus ultimately better interpret mechanisms such as gene expression (turning genes off and on).