The pattern of actin expression in human fibroblast × mouse muscle heterokaryons suggests that human muscle regulatory factors are produced

Abstract

The expression of previously dormant human muscle genes encoding two major components of the contractile apparatus was activated in multinucleated heterokaryons formed by the fusion of mouse muscle cells and human fibroblasts. The accumulation of human and mouse α-cardiac and α-skeletal actin transcripts was compared by Northern blot, slot blot, and S1 nuclease assays. The pattern of human transcript accumulation in heterokaryons was quite distinct from that in the mouse muscle cells that induced it, and strikingly similar in time course and relative amounts to that in human primary muscle cultures. In addition, the usual decline in the level of mouse α-cardiac actin transcripts was not observed; instead, after fusion with human fibroblasts the levels increased. Our findings suggest that the activated human nuclei in heterokaryons produce their own muscle regulatory factors that alter the expression of mouse muscle genes and direct the expression of the human muscle phenotype.