Architecture of the Cell Nucleus

Our interest in investigating the structural organization of the nucleus is to reveal topological parameters which affect genome activity. The central player of nuclear integrity is chromatin, which is the DNA packed by histones and other factors. In addition to the task of information management, i.e. the maintenance of the genetic code and its transcription, chromatin as a complex polymer has the potential for structural organization of itself as well as the rest of the nucleus. Thus, in interphase, heterochromatin and euchromatin are two structural organizations of chromatin. The denser pack of heterochromatin correlates with transcriptional inactivation, indicating that physical accessibility is a parameter of chromatin activity. Chromosomes in interphase are organized in territories with little or no overlap. We have shown that active genomic regions preferentially localize to the surface of chromosome territories. These observations are in agreement with our working hypothesis of a functional nuclear compartment between chromosome territories, the interchromosomal domain (ICD) compartment (Zirbel et al. 1993), which states that due to facilitated accessibility RNA transcription, splicing and transport are bound to the ICD compartment. We showed further, that nuclear compounds like the endogenous Cajal bodies, PML bodies and SC35-speckles as well as ectopically expressed, physiologically inactive structures such as particles formed by Mx1-YFP or filament bundles formed by NLS-vimentin, are restricted to the ICD compartment and accumulate there. Our research focuses on the specific distribution of chromatin in the interphase nucleus, its differential accessibility and its temporal flexibility.

<- Fig. 2: Active genes locate preferentially to the surface of chromosome territories: Left: Confocal sections of human myotube nuclei co-hybridized with a chromosome 2-specific painting probe (green) and a probe for the active gene-locus of nebulin on 2q23.2 (red). Right: 3D volume-rendered model of the two chromosome territories. Scale bar 2µm. Active genes locate preferentially to the surface of chromosome territories: Left: Confocal sections of human myotube nuclei co-hybridized with a chromosome 2-specific painting probe (green) and a probe for the active gene-locus of nebulin on 2q23.2 (red). Right: 3D volume-rendered model of the two chromosome territories. Scale bar, 2 µm (Scheuermann et al. 2004, ECR 301: 266).