Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Mesoscale Modeling Predicts New Polymorphic Structure of Chromatin
Our genomic DNA achieves cellular compaction through several hierarchical levels of organization. First, DNA wraps around certain protein spools called nucleosomes that comprise of positively charged proteins called histones. The resulting "bead-on-a-string" nucleoprotein complex folds further into a 30-nm chromatin fiber at physiological conditions in the presence of another protein called the linker histone. The thermodynamic and structural details of how histone proteins and magnesium ions critically compact and modulate chromatin structure as well as regulate gene transcription are not well understood. In this talk, I will present the development of a new mesoscopic model of chromatin that reproduces experimental data, elucidates the physical role of each histone in chromatin folding, and proposes a new polymorphic structure of chromatin. Specifically, we show that the linker histone promotes a two-start zigzag structure of chromatin dominated by interactions between alternate nucleosomes. Divalent ions like Mg2+ further compact the fiber by significantly screening the repulsion among linker DNAs and promoting their bending, thus allowing them to better accommodate at the fiber axis. Our results thus reconcile the zigzag topology with linker DNA bending characteristic of the solenoid topology in a single polymorphic chromatin fiber structure. Development of this model now opens up new avenues for studying the formation of higher-order structures of chromatin for studying epigenetic silencing, and the role of posttranslational modifications and variants of histones in gene regulation.
Department of Nanoengineering