Latino Studies at New York University

Antoni Luque

Biomath Group
Department of Chemistry
New York University

April 15, 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 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. However, the intermediate scales remain elusive. Here, we 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. After reviewing our previous achievements, we will present a refined linker histone model that captures, for the first time, the spontaneous condensation of its intrinsically disordered C-terminal domain upon nucleosome binding and its impact on chromatin structure. This model is in excellent agreement with independent experiments and provides a framework to understand local and global mechanisms regulating chromatin organization.