Effects of Fluctuation of Chromosome Conformation and Spatial Arrangement of Genes on the Pattern of Gene Expression

Abstract

Recently, conformation of all chromosomes in the interphase nucleus of budding yeast has been inferred from the Chromosome Conformation Capture-on-Chip (4C) data (Duan et al., Nature (2010)). However, it has not yet been ascertained how the conformational fluctuation around their mean structures affects the regulation of gene expression. To clarify this issue, we developed a dynamical structural model of interphase chromosomes in budding yeast (Tokuda et al., Biophys. J. (2012)). In the present paper, the effects of the conformational fluctuation and the arrangement of genes on the pattern of gene expression are discussed by using this coarse-grained chromosome model. In particular, the observed difference in the pattern of gene expression between the yku70 esc1 mutant which abrogates telomere anchoring and the wild-type strain (Taddei et al., Genome Res. (2009)) is studied. In the data of Taddei et al., 32 genes are expressed at higher levels and 28 genes are expressed at lower levels in the yku70 esc1 mutant than in the wild-type strain. We examine the reason of this misregulation by comparing the fluctuation of the chromosome conformation and spatial arrangement of genes in the case that telomeres are not anchored to the nuclear periphery with that in the anchored case.