June 3, 2005
NYU Chemists Use Computer Simulation to Enhance Understanding of DNA Transcription
New York University chemists have employed a computer simulation whose results have enhanced scientific understanding of the DNA transcription process. The study, funded by the National Institutes of Health, appears in the June 7 issue of the Proceedings of the National Academy of Sciences.
Previous research has indicated that chromatin--a chromosome's substance consisting of histone proteins and DNA--exhibits 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 chemists Tamar Schlick, 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 that the structure of chromatin strongly depends on its salt environment.
To Schlick and her colleagues, these results 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 to understand the mechanism of gene expression and silencing.
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