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Science 4 August 1989:
Vol. 245. no. 4917, pp. 532 - 536
DOI: 10.1126/science.2547249
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Articles

Science, Vol 245, Issue 4917, 532-536
Copyright © 1989 by American Association for the Advancement of Science

articles

5-bromo-2'-deoxyuridine blocks myogenesis by extinguishing expression of MyoD1

SJ Tapscott, AB Lassar, RL Davis, and H Weintraub

Department of Genetics, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.

The pyrimidine analog 5-bromodeoxyuridine (BUdR) competes with thymidine for incorporation into DNA. Substitution of BUdR for thymidine does not significantly affect cell viability but does block cell differentiation in many different lineages. BUdR substitution in a mouse myoblast line blocked myogenic differentiation and extinguished the expression of the myogenic determination gene MyoD1. Forced expression of MyoD1 from a transfected expression vector in a BUdR-substituted myoblast overcame the block to differentiation imposed by BUdR. Activation of BUdR-substituted muscle structural genes and apparently normal differentiation were observed in transfected myoblasts. This shows that BUdR blocks myogenesis at the level of a myogenic regulatory gene, possibly MyoD1, not by directly inhibiting the activation of muscle structural genes. It is consistent with the idea that BUdR selectively blocks a class of regulatory genes, each member of which is important for the development of a different cell lineage.


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