The laboratory studies the relationship between the genomic component (DNA) of the cell nucleus and non-genomic (protein) components from the structural and functional standpoint. To achieve proper transcription of DNA-coded genetic information in a “comprehensible” message, that will be further translated into cell’s functional proteins, DNA must fulfill two necessary conditions: it must be mobile (i.e. “to be at the right place at the right time”) and accessible (i.e. “readable”) to the appropriate proteins or protein complexes. This requires the presence in the nucleus of distinct proteins that act on the mobility and accessibility of DNA (structural elements) and proteins that can read and transcribe the information content. Studies on the relationship between nuclear structure and function have allowed the identification of typical cytoplasmic proteins in the nucleus. As a consequence, new mechanistic models of nuclear functions have been developed, based on the dynamic interaction of structural and functional nuclear components. It will be challenging, in the next few years, to understand how these different models may be integrated to develop a comprehensive picture of nuclear functions and how such models will affect the studies on human pathologies.