IDENTIFICATION AND CHARACTERIZATION OF DROSOPHILA RELATIVES OF THE YEAST TRANSCRIPTIONAL ACTIVATOR SNF2/SWI2

IDENTIFICATION AND CHARACTERIZATION OF DROSOPHILA RELATIVES OF THE YEAST TRANSCRIPTIONAL ACTIVATOR SNF2/SWI2
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DOI:
10.1128/mcb.14.4.2225
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发表时间:
1994-04-01
影响因子:
5.3
通讯作者:
TAMKUN, JW
TAMKUN, JW
中科院分区:
生物学2区
文献类型:
--
作者:
ELFRING, LK;DEURING, R;TAMKUN, JW

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果蝇brahma(brm)基因编码同源异型基因的激活因子,其与酵母转录激活因子SWI 2(SNF 2)(一种潜在的解旋酶)高度相关。为了确定brm是否是SWI 2的功能同源物,或者仅仅是SWI 2相关基因家族的一员,我们寻找了与SWI 2相关的其他果蝇基因,并在酵母细胞中研究了它们的功能。除了brm,我们还发现了SWI 2的另一个果蝇亲戚:密切相关的ISWI基因。1,027个残基的ISWI蛋白含有SWI 2蛋白家族特有的DNA依赖性ATP酶结构域,但缺乏brm和SWI 2共有的其他三个结构域。相反,ISWI蛋白在其整个长度上与人hSNF 2L蛋白高度相关(70%相同),表明它们可能是功能同源物。brm和SWI 2的DNA依赖性ATP酶结构域,但不是ISWI,在功能上是可互换的;嵌合SWI 2-brm蛋白部分挽救了swi 2-细胞的缓慢生长,并支持在酵母细胞中由糖皮质激素受体介导的体内转录激活。这些发现表明,brm是最接近的果蝇亲属SWI 2,并建议brm和SWI 2在转录激活中发挥类似的作用。
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.