Acetyl-CoA carboxylase-α: Gene structure-function relationships1

Acetyl-CoA carboxylase-α (ACC-α) is a key enzyme in the regulation of fatty acid synthesis and is subject to both acute control, via reversible phosphorylation, and chronic control that results in the regulation of synthesis of the enzyme. The gene for ACCα is expressed ubiquitously, but expression is highest in lipogenic tissues: adipose, liver, and lactating mammary gland. These tissues demonstrate a metabolic adaptation to changing physiological demands; for example, during lactation fatty acid synthesis in adipose tissue is markedly repressed, resulting in the partitioning of lipogenic precursors to the mammary gland. Lipogenic tissues can also exhibit dysfunctions that result in excess fat deposition in farm animals and obesity in humans. Transcription of the ACC-α gene is initiated from multiple promoters in a tissue-specific fashion. Promoter II (PII) transcripts are present in all tissues, whereas promoter I (PI) transcripts are principally restricted to adipose tissue. We have also identified an additional promoter (PIII) that is also expressed in a