Location of a topologically associating domain at the nuclear periphery has no systematic causal effect on its genes transcription levels in drosophila nuclei.

Abstract

Several studies have demonstrated a correlation between expression of genes and their positioning at the nuclear periphery. However, no systematic genome-wide analysis of how the probability of location at the nuclear envelope (NE) affects gene expression is available. It is unclear whether there is a genome-wide correlation or causal relationship between the expression levels of groups of genes in topologically associating domains (TADs) of Drosophila nuclei and the probabilities of TADs to be found at the NE. To investigate the possible relationship, we have developed a coarse-grained dynamic model of the entire Drosophila melanogaster interphase nucleus that explicitly accounts for the different epigenetic classes of TADs and for the interactions between the NE and lamina-associated domains (LADs). The model predicts a highly dynamic positioning of LADs and TADs at the NE. The probability of a LAD-containing TAD to be found at the NE is determined by a highly variable local density of LADs along genome. Modeling of the lamin depleted nuclei predicts a significant reduction of TAD contacts with the NE and a substantial redistribution of the chromatin. We combine model derived probabilities of TADs to be found at the NE with the genome-wide experimental gene expression data for both wild type and lamin depleted nuclei. The analysis of the TAD averaged gene transcription levels against the probabilities of individual TADs to be at the NE suggests that, within statistical error margin, the stochastic positioning of Drosophila TADs at the NE does not, by itself, systematically affect the average level of gene expression in TADs. A weak anti-correlation exists between these expression levels and the probabilities of TADs to be found at the NE, but no causality.