Rosenkrantz M, Kell C S, Pennell E A, Devenish L J
Department of Microbiology and Immunology, Virginia Commonwealth University/Medical College of Virginia, Richmond 23298-0678.
Mol Microbiol. 1994 Jul;13(1):119-31. doi: 10.1111/j.1365-2958.1994.tb00407.x.
The yeast nuclear gene CIT1 encodes mitochondrial citrate synthase, which catalyses the first and rate-limiting step of the tricarboxylic acid (TCA) cycle. Transcription of CIT1 is subject to glucose repression. Mutations in HAP2, HAP3 or HAP4 block derepression of a CIT1-lacZ gene fusion. The HAP2,3,4 transcriptional activator also activates nuclear genes encoding components of the mitochondrial electron transport chain, and thus it co-ordinates derepression of two major mitochondrial functions. Two DNA sequences resembling the consensus HAP2,3,4-binding site (ACCAATNA) are located at approximately -310 and -290, upstream of the CIT1 coding sequence. Deletion and mutation analysis indicates that the -290 element is critical for activation by HAP2,3,4. Glucose-repressed expression of CIT1 is largely independent of HAP2,3,4, is repressed by glutamate, and requires a DNA sequence between -367 and -348. Evidence is presented for a second HAP2,3,4-independent activation element located just upstream and overlapping the -290 HAP2,3,4 element.
酵母核基因CIT1编码线粒体柠檬酸合酶，该酶催化三羧酸（TCA）循环的第一步及限速步骤。CIT1的转录受到葡萄糖阻遏。HAP2、HAP3或HAP4中的突变会阻断CIT1 - lacZ基因融合的去阻遏。HAP2、3、4转录激活因子还可激活编码线粒体电子传递链组分的核基因，因此它可协调两种主要线粒体功能的去阻遏。两个类似于共有HAP2、3、4结合位点（ACCAATNA）的DNA序列位于CIT1编码序列上游约-310和-290处。缺失和突变分析表明，-290元件对于HAP2、3、4的激活至关重要。CIT1的葡萄糖阻遏表达在很大程度上不依赖于HAP2、3、4，受谷氨酸抑制，并且需要-367至-348之间的DNA序列。有证据表明，在-290 HAP2、3、4元件上游且与之重叠的位置存在第二个不依赖于HAP2、3、4的激活元件。
