REGULATED EXPRESSION OF THE GAL4 ACTIVATOR GENE IN YEAST PROVIDES A SENSITIVE GENETIC SWITCH FOR GLUCOSE REPRESSION
REGULATED EXPRESSION OF THE GAL4 ACTIVATOR GENE IN YEAST PROVIDES A SENSITIVE GENETIC SWITCH FOR GLUCOSE REPRESSION
复制标题
DOI：
10.1073/pnas.88.19.8597
复制
发表时间：
1991-10-01
影响因子：
11.1
通讯作者：
JOHNSTON, M
中科院分区：
文献类型：
--
作者：
GRIGGS, DW;JOHNSTON, M
葡萄糖（分解代谢物）抑制由多种机制介导，所述多种机制联合收割机在至少千倍范围内调节GAL基因的转录。 我们已经确定，这主要是由于适度的葡萄糖抑制（4至7倍）的GAL 4，基因编码的GAL基因的转录激活因子的表达。GAL 4调节受先前参与葡萄糖抑制途径的几个基因突变的影响;它不依赖于GAL 4或GAL 80蛋白功能。 发现GAL 4启动子序列介导葡萄糖抑制，位于可能是“TATA盒”的正作用元件的下游。“在这个区域中可能是MIG 1蛋白结合位点的两个几乎相同的序列（10/12碱基对）被鉴定为功能性葡萄糖控制元件。 在这些位点之一中的4个碱基对插入导致组成型GAL 4合成，并导致GAL 1表达的葡萄糖抑制的实质性缓解（50倍）。 此外，适度降低GAL 4表达的启动子缺失，因此推测GAL 4蛋白合成的量，引起GAL 1表达的更大降低。 这些结果表明，GAL 4协同激活GAL 1的表达。 因此，GAL 1表达的葡萄糖抑制主要是由于GAL 4转录减少引起的GAL 4蛋白水平相对较小的降低。 这说明了弱表达调控基因的适度调控如何作为敏感的遗传开关，对环境变化产生极大的放大反应。
Glucose (catabolite) repression is mediated by multiple mechanisms that combine to regulate transcription of the GAL genes over at least a thousandfold range. We have determined that this is due predominantly to modest glucose repression (4- to 7-fold) of expression of GAL4, the gene encoding the transcriptional activator of the GAL genes. GAL4 regulation is affected by mutations in several genes previously implicated in the glucose repression pathway; it is not dependent on GAL4 or GAL80 protein function. GAL4 promoter sequences that mediate glucose repression were found to lie downstream of positively acting elements that may be "TATA boxes." Two nearly identical sequences (10/12 base pairs) in this region that may be binding sites for the MIG1 protein were identified as functional glucose-control elements. A 4-base-pair insertion in one of these sites causes constitutive GAL4 synthesis and leads to substantial relief (50-fold) of glucose repression of GAL1 expression. Furthermore, promoter deletions that modestly reduce GAL4 expression, and therefore presumably the amount of GAL4 protein synthesized, cause much greater reductions in GAL1 expression. These results suggest that GAL4 works synergistically to activate GAL1 expression. Thus, glucose repression of GAL1 expression is due largely to a relatively small reduction of GAL4 protein levels caused by reduced GAL4 transcription. This illustrates how modest regulation of a weakly expressed regulatory gene can act as a sensitive genetic switch to produce greatly amplified responses to environmental changes.