Redistribution of nuclear lamin A is an early event associated with differentiation of human promyelocytic leukemia HL-60 cells.
The nuclear lamina of mammalian somatic cells is characterized by the constitutive presence of lamin B polypeptides while the appearance of lamins A and C generally occur during establishment of a differentiated phenotype. We have used antibodies specific to the unique carboxy-terminal domain of lamin A, i.e. distinct from the shared domains of lamins A and C, to study the individual behaviour of lamin A during establishment of a macrophage phenotype in human HL-60 cells. Lamin A was present as a nuclear cap in the majority of undifferentiated cells and it was redistributed to a full peripheral nuclear location very early after induction of differentiation by phorbol esters, even in the presence of a protein synthesis inhibitor. Induction of the cells into a reversible precommitment state by bromodeoxyuridine was accompanied by a similar redistribution of lamin A that however reverted to a cap after removal of inducer. No changes were observed in the uniform peripheral nuclear location of lamin C under all of these conditions. These results strongly suggest that lamin A plays a role in the early events of cell differentiation. Taken together with previous results on the interaction of A-type lamins with chromatin, these findings offer experimental evidence consistent with the proposed role of A-type lamins, and particularly lamin A, in the process of chromatin reorganization that accompanies the expression of a differentiated phenotype.
Collard
J F
JF
Institut du Cancer de Montréal, Hôpital Notre-Dame, Québec, Canada.
Senécal
J L
JL
Raymond
Y
Y
D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D034904:Lamin Type A; D034921:Lamin Type B; D034882:Lamins; D015473:Leukemia, Promyelocytic, Acute; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism
D034904:Lamin Type A; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D014746:Vimentin; C440308:lamin C; D003513:Cycloheximide; D001973:Bromodeoxyuridine; D013755:Tetradecanoylphorbol Acetate