Figure 3. An integrated approach for mechanistic insights into nuclear structure-gene expression interrelationships.

Knowledge of co-regulatory factors that interact with scaffolding proteins obtained by the combined application of cellular, biochemical, and molecular approaches provides basis for developing an interactome for each scaffolding protein (top left panel). Components of the interactome can be visualized, albeit to a limited extent, by in situ immunofluorescence microscopy. Such “proteomics” approach provides mechanistic insight into combinatorial control of gene expression in normal and cancer cells. In parallel, genome-wide profiles can be generated that reflect changes in gene expression during tumorigenesis (“genomics”; bottom left panel). Importantly, newly developed mathematical algorithms can identify unique quantitative signatures for regulatory proteins (Right panel, “intranuclear informatics”) and apply subtle changes in these ‘architectural signatures’ to distinguish normal proteins (e.g. WT Runx2) from subnuclear targeting deficient variants (e.g. mSTD Runx2). Such an integrated approach is required to gain mechanistic insights into nuclear structure-gene expression interrelationships for biological control as well as for cancer diagnosis and treatment.