Antinuclear antibodies as probes to explore the structural organization of the genome

Certain DNA binding proteins are thought to organize the mammalian genome into distinct 3 dimensional structures, each characteristic of a given differentiated state. Autoantibodies to 2 types of DNA binding protein complexes, the nuclear lamina and p70/p80 (Ku), were identified in sera of patients with collagen vascular diseases. The intranuclear distribution, DNA binding, and behavior during mitosis of these antigens were examined using autoimmune sera and murine monoclonal antibodies. In vivo, the antigens have different intranuclear distributions and solubility characteristics. However, both antigens appear to reversibly bind to DNA during interphase and to rapidly dissociate from DNA during mitosis. Although the binding affinity of p70/p80 to DNA is heterogeneous, the interaction between p70/p80 and DNA in vitro is stable over 2 h or more. The rapid dissociation of p70/p80 from DNA during mitosis may therefore be mediated by a modification in either chromatin structure or in the p70/p80 antigen itself. Other proteins that reversibly interact with DNA, such as the lamins and nuclear pores, may have a role in the organization of DNA into transcribable euchromatin and nontranscribable heterochromatin. Autoantibodies to these proteins, and possibly those reactive with p70/p80, or other DNA binding proteins may be useful probes for studying both chromatin organization and the causes of autoimmune diseases such as systemic lupus erythematosus.