In VivoRegulation of the Activity of the Two Promoters of the Rat Acetyl Coenzyme-A Carboxylase Gene*

Abstract

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.

Direct Role of ChREBP·Mlx in Regulating Hepatic Glucose-responsive Genes

“…Acetyl-CoA mRNA is induced in mammalian liver after a high carbohydrate diet (32,33). Because we had found that (48) that was used as a positive control for the His-tag antibody in this experiment.…”

The Rat Pyruvate Carboxylase Gene Structure

“…On the other hand, the proximal promoter lacks a TATA or CAAT box, thus exhibiting features of a housekeeping promoter. Transcripts produced from this type of promoter are expressed constitutively (43). In addition, when transcripts are generated from two promoters, they have been shown to have different translation efficiencies (44).…”

Cloning and characterization of the 5′ end and promoter region of the chicken acetyl-CoA carboxylase gene

“…However, administration of insulin to streptozotocindiabetic rats further activates both promoters, regardless of the type of diet given to the starved animals [27]. In contrast, only PI -and not PII -responds to nutritional induction in white adipose tissue [28]. It has been shown recently that the CCAAT\ enhancer-binding protein (C\EBP) may be one of the factors that is responsible for the activation of promoter PI under lipogenic conditions [29].…”