López-Casillas F, Ponce-Castañeda M V, Kim K H
Biochemistry Department, Purdue University, West Lafayette, Indiana 47907.
Endocrinology. 1991 Aug;129(2):1049-58. doi: 10.1210/endo-129-2-1049.
The acetyl-coenzyme-A carboxylase (ACC) gene contains two promoters: promoter I (PI) and promoter II (PII). Depending upon which promoter is active, two classes of ACC mRNA are formed. The physiological significance of the presence of two promoters in the gene is not clear at this time. However, this question can be indirectly approached by examination of their expression patterns under different physiological conditions. We have examined the activities of these two promoters under different physiological conditions by means of primer extension analysis. Under normal conditions, the Wistar rat, fed standard chow ad libitum, expresses only basal levels of PI in white adipose tissue and PII in the liver. Starvation leads to the virtual disappearance of transcriptional products from these promoters. When fatty acid synthesis is stimulated by refeeding a fat-free diet to starved rats, both PI and PII are activated in the liver; however, in white adipose tissue, only PI, not PII, is responsive to this nutritional induction. On the other hand, in streptozotocin-diabetic rats, in which the activity of both promoters in both tissues is depressed, the administration of insulin quickly induces PI in adipose tissues, but has no significant effect on either of the promoters in the liver. During the weaning transition, the increase in hepatic lipogenesis is accompanied by activation of PI and PII when the pups are weaned onto a fat-free diet. Weaning onto a standard chow causes only a slight increase in PII. During the lactation period, profound alterations occur in the metabolism of the lipogenic tissues. In the lactating rat mammary gland only PII is active, and its activity is increased throughout lactation, reaching a plateau by day 7. Concomitantly, all ACC gene activity is completely shut off in the adipose tissue, while in the liver, PII, the only promoter active, is affected only minimally. The fat accumulation of the genetically obese Zucker rats is largely due to an abnormally high hepatic lipogenesis. In the obese Zucker rat (fa/fa), the level of expression of PII is similar to that in its lean siblings; however, PI is constitutively expressed at high levels, comparable to those in the Wistar rat that has been subjected to the starvation/refeeding induction. These studies demonstrate that the in vivo transcriptional control of the dual promoter rat ACC gene is a highly regulated and tissue-specific process.
乙酰辅酶A羧化酶（ACC）基因包含两个启动子：启动子I（PI）和启动子II（PII）。根据哪个启动子具有活性，可形成两类ACC mRNA。目前尚不清楚该基因中存在两个启动子的生理意义。然而，这个问题可以通过检查它们在不同生理条件下的表达模式来间接探讨。我们通过引物延伸分析研究了这两个启动子在不同生理条件下的活性。在正常情况下，随意喂食标准饲料的Wistar大鼠在白色脂肪组织中仅表达基础水平的PI，在肝脏中表达PII。饥饿导致这些启动子的转录产物几乎消失。当给饥饿的大鼠重新喂食无脂饮食以刺激脂肪酸合成时，PI和PII在肝脏中均被激活；然而，在白色脂肪组织中，只有PI对这种营养诱导有反应，PII则无反应。另一方面，在链脲佐菌素诱导的糖尿病大鼠中，两个组织中两个启动子的活性均降低，给予胰岛素可迅速诱导脂肪组织中的PI，但对肝脏中的任何一个启动子均无显著影响。在断奶过渡期，当幼崽断奶改为无脂饮食时，肝脏脂肪生成的增加伴随着PI和PII的激活。断奶改为标准饲料仅导致PII略有增加。在哺乳期，脂肪生成组织的代谢发生深刻变化。在泌乳大鼠的乳腺中只有PII具有活性，并且其活性在整个哺乳期都增加，到第7天达到平台期。与此同时，脂肪组织中所有ACC基因活性完全关闭，而在肝脏中，唯一具有活性的启动子PII仅受到最小程度的影响。遗传性肥胖的Zucker大鼠的脂肪积累很大程度上归因于肝脏脂肪生成异常高。在肥胖的Zucker大鼠（fa/fa）中，PII的表达水平与其瘦同胞相似；然而，PI组成性地高水平表达，与经历饥饿/再喂食诱导的Wistar大鼠相当。这些研究表明，双启动子大鼠ACC基因的体内转录调控是一个高度调节且具有组织特异性的过程。
