Postdoc, Schlick Lab, Chemistry Department, New York University
New position (January): Assistant Professor at the Viral Information Institute and the Mathematics & Statistics Department, San Diego State University
September 9, 2014
September 9, 2014
Role of linker histones in the structure and dynamics of chromatin fibers
In humans, each cell stores two meters of genomic DNA in the nucleus, where a cohort of proteins such as core histones and linker histones is responsible for DNA's condensation and genetic activity. This macromolecular complex called chromatin is also present in the rest of eukaryotes. Chromatin is composed of nucleosomes, nanometric beads made of DNA and eight core histones. These nucleosomes are linked together by DNA in chromatin fibers and fold into hierarchical structures to form the chromosomes. Experimental techniques have characterized at great detail the structure of chromatin at the nucleosome and chromosome level. The intermediate scales of chromatin, however, remain elusive. Here, I will present a computational model that captures the mesoscale properties of chromatin fibers. This approach has elucidated relevant molecular mechanisms in the past decade, and continuous improvements of the model has provided valuable insights into the complex organization of chromatin. In this talk I will introduce a refined linker histone model that captures the spontaneous condensation of its intrinsically disordered C-terminal domain upon nucleosome binding and the impact of linker histone on chromatin structure. This model is in excellent agreement with independent experiments and provides a framework to understand local and global mechanisms regulating, for instance, post-translational modifications and the linker DNA length, in chromatin organization.