The signal for glucose repression of the lactose-galactose regulon is amplified through subtle modulation of transcription of the Kluyveromyces lactis Kl-GAL4 activator gene.
The signal for glucose repression of the lactose-galactose regulon is amplified through subtle modulation of transcription of the Kluyveromyces lactis Kl-GAL4 activator gene.
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通过微妙调节乳酸克鲁维酵母 K1-GAL4 激活基因的转录，放大乳糖-半乳糖调节子的葡萄糖抑制信号。
DOI：
10.1128/mcb.12.5.1924-1931.1992
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发表时间：
1992
影响因子：
5.3
通讯作者：
Dickson,RC
中科院分区：
文献类型：
--
作者：
Kuzhandaivelu,N;Jones,WK;Martin,AK;Dickson,RC
乳糖-半乳糖调节的诱导被葡萄糖强烈抑制，但不是所有菌株的乳酸克卢维菌。我们在这里表明，在强烈抑制的菌株中，kl - gal4mrna的合成减少了2到3倍，并且调节中的结构基因（如β-半乳糖苷酶的结构基因lac4）的表达下调了40倍或更多。对具有强或弱抑制表型的菌株的比较分析显示，kl - gal4（也称为lac9）阳性调节基因的启动子存在两个碱基的差异。这两个碱基的差异是造成强抑制表型和弱抑制表型的原因。这两个碱基变化对称地位于具有部分双重旋转对称的DNA序列中（21个碱基中的14个）。我们假设这个区域作为一个敏感的调节开关，一个上游抑制序列（URS）。根据我们的模型，培养基中葡萄糖的存在，通过一种未知的途径，信号抑制蛋白结合URS。结合降低了kl - gal4基因的转录，使K1-GAL4蛋白的浓度低于诱导flac4和调控子中其他基因所需的水平。对于表现出弱葡萄糖抑制的菌株，我们假设URS的两个碱基变化减少了抑制因子的结合，因此调节因子不被抑制。我们的研究结果说明了遗传调控的一个重要原则：调节蛋白浓度的微小变化（2- 3倍）可以产生结构基因表达的巨大变化（40倍或更大）。这种信号放大机制可能在许多需要调节转录的生物现象中发挥作用。
Induction of the lactose-galactose regulon is strongly repressed by glucose in some but not all strains ofKluyveromyces lactis.We show here that in strongly repressed strains, two to three times lessKl-GAL4mRNA is synthesized and that expression of structural genes in the regulon such asLAC4, the structural gene for β-galactosidase, is down regulated 40-fold or more. Comparative analysis of strains having a strong or weak repression phenotype revealed a two-base difference in the promoter of theKl-GAL4(also calledLAC9) positive regulatory gene. This two-base difference is responsible for the strong versus the weak repression phenotype. The two base changes are symmetrically located in a DNA sequence having partial twofold rotational symmetry (14 of 21 bases). We hypothesize that this region functions as a sensitive regulatory switch, an upstream repressor sequence (URS). According to our model, the presence of glucose in the culture medium signals, by an unidentified pathway, a repressor protein to bind the URS. Binding reduces transcription of theKl-GAL4gene so that the concentration of the K1-GAL4 protein falls below the level needed for induction ofLAC4and other genes in the regulon. For strains showing weak glucose repression, we hypothesize that the two base changes in the URS reduce repressor binding so that the regulon is not repressed. Our results illustrate an important principle of genetic regulation: a small (2- to 3-fold) change in the concentration of a regulatory protein can produce a large (40-fold or greater) change in expression of structural genes. This mechanism of signal amplification could play a role in many biological phenomena that require regulated transcription.