Tapscott S J, Lassar A B, Davis R L, Weintraub H
Department of Genetics, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Science. 1989 Aug 4;245(4917):532-6. doi: 10.1126/science.2547249.
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.
嘧啶类似物5-溴脱氧尿苷（BUdR）与胸腺嘧啶竞争掺入DNA。用BUdR替代胸腺嘧啶不会显著影响细胞活力，但会阻断许多不同谱系中的细胞分化。在小鼠成肌细胞系中用BUdR替代可阻断肌源性分化并消除肌源性决定基因MyoD1的表达。在经BUdR替代的成肌细胞中，通过转染的表达载体强制表达MyoD1克服了由BUdR施加的分化阻滞。在转染的成肌细胞中观察到BUdR替代的肌肉结构基因的激活以及明显正常的分化。这表明BUdR在肌源性调节基因水平上阻断肌生成，可能是MyoD1，而不是通过直接抑制肌肉结构基因的激活。这与BUdR选择性阻断一类调节基因的观点一致，其中每个成员对不同细胞谱系的发育都很重要。
