Chromosomes occupy territories within nuclei, where they fold into looped structures, including large-scale compartments and smaller topologically associated domains. An open question is whether and how higher-order chromosome conformation impacts transcriptional processes. We recently developed iterative DNA FISH methodology (“chromosome tracing”) to define the conformation of chromosomes, or regions of chromosomes, in single cells of C. elegans (Sawh et al., Molecular Cell, 2020). We will use this method to examine the relationship between chromosome morphology and gene expression in two biological contexts. In Aim 1 we will explore the interconnection between chromosome conformation and genes that undergo intermittent transcriptional activation (bursting). In Aim 2, we will examine dosage compensation and its dependence on X chromosome morphology, in collaboration with Barbara Meyer (Univ of California - Berkeley, USA) and Peter Meister (Univ of Bern, CH). These studies will lay a foundation for understanding the role of chromosome organization in C. elegans transcription at the single cell level.