Expression of muscle genes in heterokaryons depends on gene dosage.
We report that gene dosage, or the ratio of nuclei from two cell types fused to form a heterokaryon, affects the time course of differentiation-specific gene expression. The rate of appearance of the human muscle antigen, 5.1H11, is significantly faster in heterokaryons with equal or near-equal numbers of mouse muscle and human fibroblast nuclei than in heterokaryons with increased numbers of nuclei from either cell type. By 4 d after fusion, a high frequency of gene expression is evident at all ratios and greater than 75% of heterokaryons express the antigen even when the nonmuscle nuclei greatly outnumber the muscle nuclei. The kinetic differences observed with different nuclear ratios suggest that the concentration of putative trans-acting factors significantly influences the rate of muscle gene expression: a threshold concentration is necessary, but an excess may be inhibitory.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D006822:Hybrid Cells / Q000502:physiology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics*; D009132:Muscles / Q000502:physiology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D009124:Muscle Proteins