(661d) DNA Folding and Regulation: From Nucleosomes to Chromatin to Chromosomes

In this talk, I will discuss modeling of chromatin at three different length scales, with the aim of enhancing our fundamental understanding of the organization, dynamics, and regulation of DNA within our cells. First, I will talk about high-resolution, all-atom molecular docking, molecular dynamics, and free energy studies of the H4 histone tail [1]. These studies provide novel insights into the structure of the tail bound to the acidic patch of neighboring nucleosomes and how the acetylation of lysine K16 on the histone tail could disrupt the binding interactions to trigger chromatin unfolding and subsequent transcriptional activation. Next, I will talk about an intermediate-resolution, mesoscale model [2] of chromatin that uncovers intriguing features like twist inversion and nucleosome flipping related to the propagation of torsional stresses across nucleosomes within the chromatin fiber [3]. Finally, I will talk about our recent efforts in developing low-resolution, lattice-animal models of chromosomes that represents chromosome loops at different length scales, leading to a self-similar fractal structure [4]. I will show how this model explains emerging results from genome-wide contact probability and spatial distance measurements from the HiC and FISH techniques, respectively.

[1] D. Yang and G. Arya, "Structure and binding of the H4 histone tail and the effects of lysine 16 acetylation," Phys. Chem. Chem. Phys. 13, 2911 (2011).

[2] S. Grigoryev, G. Arya, S. Correll, C. Woodcock, and T. Schlick, "Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions," Proc. Natl. Acad. Sci. 106, 13317 (2009).

[3] I. V. Dobrovolskaia, M. Kenward, and G. Arya, "Twist propagation in dinucleosome arrays," Biophys. J. 99, 3355 (2010).

[4] B. V. S. Iyer and G. Arya, “Lattice animal model of interphase chromosomes”, submitted.