Event

GBCB Seminar

Nick Kinney, GBCB Doctoral Candidate, on "Chromosome-nuclear envelope interactions have multiple effects on chromosome folding dynamics in simulation"


Advisors: Dr. Igor Sharakhov, Dept of Entomology, VT
Dr. Alexey Onufriev, Dept of Computer Science and Applications, VT

Thursday, January 29, 4:00PM, VBI Conference Center, 1015 Life Science Circle

Abstract: It is well recognized that the chromosomes of eukaryotes fold into non-random configurations within the nucleus. In humans and fruit flies, chromosomes likely adopt a particular 3D configuration called the fractal globule (FG) ( 1 ) which has multiple biologically significant properties. However, the fractal globule is a metastable state which, over time, transitions to a less biologically favorable state called the equilibrium globule ( 2 ) . One of the key questions is how the FG state is stabilized in-vivo? We use simulations to study the effects of chromosome-nuclear envelope (Chr-NE) interactions on the dynamics of the fractal globule within a model of Drosophila melanogaster (fruit fly) interphase chromosomes. The computational model represents chromosomes as self-avoiding walks (SAW) bounded by the nuclear envelope (NE). Model parameters such as nucleus size, chromosome persistence length, and chromosome-nuclear envelope interactions are taken directly from experiment(3). Several key characteristics of the non-equilibrium FG state are monitored during each simulation’s progress: chromosome territories, intra-chromosomal interaction probabilities, loci specific diffusion constants, and presence of the Rabl (polarized) chromosome arrangement. Next, we compare the outcomes of simulations which include or exclude Chr-NE interactions. We find that Chr-NE interactions reinforce the non-equilibrium properties such as chromosome territories, high intra-chromosome interaction probabilities, and the Rabl chromosome arrangement. In addition, Chr-NE interactions affect loci specific and averaged chromosomal diffusion. Based on these results we conclude that the presence of Chr-NE interactions may delay the decay of the biologically relevant fractal globule state in vivo.

References:
1. Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A. and Cavalli, G. (2012) Three-dimensional folding and functional organization principles of the Drosophila genome. Cell , 148 , 458-472 .

2. Mirny, L. (2011) The fractal globule as a model of chromatin architecture in the cell. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology , 19 , 37-51.

3. Pickersgill, H., Kalverda, B., de Wit, E., Talhout, W., Fornerod, M. and van Steensel, B. (2006) Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat Genet , 38 , 1005-1014 .