Immunocytogenetics. IV. Human autoantibodies to heterochromatin-associated proteins.
We report here a novel class of human autoantibodies with immunological affinity for constitutive heterochromatin. Indirect immunofluorescence localized different proteinaceous antigens to the AT-rich paracentromeric heterochromatin of mouse chromosomes, the GC-rich heterochromatic regions of sheep chromosomes, and the large C-banded regions of human chromosomes 1, 9, and 16. Minor amounts of the heterochromatin-associated proteins were uniformly distributed on the chromosomes of all vertebrate species. Their antigenic determinants have been highly conserved during evolution. The chromosomal distribution of the heterochromatin-associated antigens is not altered in interspecific somatic cell hybrids but apparently reflects a stable structural property germane to each chromosome type. The antigenic proteins remain bound to their respective epitopes throughout the entire cell cycle and in meiosis. The heterochromatin-associated antigens represent a major nonhistone component of the mitotic chromosome scaffold and the interphase nuclear matrix. Immunoblotting performed with a human autoimmune serum to mouse heterochromatin revealed a characteristic pattern of polypeptides with molecular weights ranging from 35 to 120 kDal. Drugs that interfere in vivo with the higher-order chromatin structure had no effect on the expression and chromosomal distribution of the heterochromatin-associated antigens. However, the antibody binding sites in chromatin can be completely masked by treating fixed cell preparations with certain DNA-binding ligands.
Haaf
T
T
Department of Human Genetics, University of Würzburg, FRG.
Dominguez-Steglich
M
M
Schmid
M
M
D000818:Animals; D000974:Antibodies, Antinuclear; D001327:Autoimmune Diseases / Q000276:immunology; D002478:Cells, Cultured; D002871:Chromosome Banding; D005455:Fluorescent Antibody Technique; D006570:Heterochromatin / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D015151:Immunoblotting; D007399:Interphase; D008024:Ligands; D008677:Metaphase
D000974:Antibodies, Antinuclear; D006570:Heterochromatin; D008024:Ligands