Elfring L K, Deuring R, McCallum C M, Peterson C L, Tamkun J W
Department of Biology, University of California, Santa Cruz 95064.
Mol Cell Biol. 1994 Apr;14(4):2225-34. doi: 10.1128/mcb.14.4.2225-2234.1994.
The Drosophila brahma (brm) gene encodes an activator of homeotic genes that is highly related to the yeast transcriptional activator SWI2 (SNF2), a potential helicase. To determine whether brm is a functional homolog of SWI2 or merely a member of a family of SWI2-related genes, we searched for additional Drosophila genes related to SWI2 and examined their function in yeast cells. In addition to brm, we identified one other Drosophila relative of SWI2: the closely related ISWI gene. The 1,027-residue ISWI protein contains the DNA-dependent ATPase domain characteristic of the SWI2 protein family but lacks the three other domains common to brm and SWI2. In contrast, the ISWI protein is highly related (70% identical) to the human hSNF2L protein over its entire length, suggesting that they may be functional homologs. The DNA-dependent ATPase domains of brm and SWI2, but not ISWI, are functionally interchangeable; a chimeric SWI2-brm protein partially rescued the slow growth of swi2- cells and supported transcriptional activation mediated by the glucocorticoid receptor in vivo in yeast cells. These findings indicate that brm is the closest Drosophila relative of SWI2 and suggest that brm and SWI2 play similar roles in transcriptional activation.
果蝇的brahma（brm）基因编码一种同源异型基因激活因子，该因子与酵母转录激活因子SWI2（SNF2）高度相关，SWI2是一种潜在的解旋酶。为了确定brm是SWI2的功能同源物还是仅仅是SWI2相关基因家族的一员，我们搜索了与SWI2相关的其他果蝇基因，并在酵母细胞中检测了它们的功能。除brm外，我们还鉴定出另一个SWI2的果蝇相关基因：密切相关的ISWI基因。1027个氨基酸残基的ISWI蛋白含有SWI2蛋白家族特有的依赖DNA的ATP酶结构域，但缺少brm和SWI2共有的其他三个结构域。相反，ISWI蛋白在其全长上与人类hSNF2L蛋白高度相关（70%相同），表明它们可能是功能同源物。brm和SWI2的依赖DNA的ATP酶结构域在功能上是可互换的，但ISWI的不行；一种嵌合的SWI2-brm蛋白部分挽救了swi2-细胞的缓慢生长，并在酵母细胞体内支持糖皮质激素受体介导的转录激活。这些发现表明brm是果蝇中与SWI2关系最密切的基因，并表明brm和SWI2在转录激活中发挥相似作用。
