Nucleocytoplasmic Interactions And The Control Of Nuclear Activity

The nuclei of mature chick erythrocytes are genetically inactive and do not synthesize RNA, DNA, or protein. In heterokaryons formed by fusing chick red cells with human HeLa cells, the erythrocyte nucleus is reactivated, grows in size, and resumes RNA synthesis. The reactivation process occupies several days after cell fusion and results in the synthesis of new chick specific protein. The signals activating the chick genome appear to operate at several different levels. Early changes in the physicochemical properties of chick deoxyribonucleoprotein appear to be triggered by changes in the ionic environment. Nuclear growth during the first two days after fusion is due mainly to an accumulation in the chick nucleus of human nucleospecific molecules, probably proteins. These proteins are taken up from the surrounding HeLa cytoplasm or directly from HeLa nuclei lying in close contact with the chick nuclei. With increasing numbers of chick erythrocyte nuclei in the cytoplasm, less human nucleospecific proteins accumulate in each chick nucleus and the rate at which RNA synthesis accelerates is slowed down. By reactivating chick erythrocyte nuclei in the cytoplasms of rat and mouse cells representing different lines of cell differentiation, attempts have been made to study how the cytoplasm influences the phenotype expressed by the reactivated chick erythrocyte nucleus. Chick erythrocyte nuclei have been reactivated in rat myoblasts and myotubes at a time when rat myosin synthesis starts. No significant chick myosin synthesis has been demonstrated in spite of the fact that the chick erythrocyte nuclei developed a nucleolus, produced RNA, and expressed other chick genes in the form of chick antigens. Hybrids made by fusing chick myoblasts with rat myoblasts, however, synthesized both chick and rat myosin