(717e) Coarse-Grained Modeling of Heterochromatin Formation in Chromosomal DNA

Historically, the central dogma of genetics asserts that DNA sequence holds all of the necessary biological information. However, two organisms with identical genetic information may have different behavior due to chemical modifications in their genome packaging. This notion of epigenetic regulation represents a paradigm change in how we think about genetic traits. To establish a quantitative understanding of epigenetic regulation, we need to understand the conditions for chromosomal DNA to condense into regions of tightly packed heterochromatin where their expression is suppressed. At certain stages in the cell cycle, the heterochromatin appears to condense into â??fociâ? that are distributed throughout the nucleus. These observations are qualitatively reminiscent of the better understood microphase separation of traditional block copolymers. If the spatial chromatin texture is indeed governed by thermodynamics, then a wealth of knowledge from traditional polymer physics can be applied with appropriate modifications. I will present on a Monte Carlo simulation where the DNA and associated proteins are modeled as a semiflexible copolymer with blocks of increased methylation state that are preferentially bound together to cause microphase separation. To model condensation on the size scale of nucleus, we use a theoretically informed coarse graining method. As staining experiments show that heterochromatin is preferentially segregated to the periphery of the nucleus, understanding chromosomal condensation in the presence of a confinement is of particular interest. The predictions for the conditions leading to condensation and the resulting spatial and genomic patterns of condensation will be presented.