Metabolic pathways can also be regulated by transcriptional mechanisms increasing or decreasing levels of enzymes. Take the example of lipid metabolism. The Sterol Regulatory Element Binding Protein (SREBP) transcription factors are the master regulators that control the expression of nearly all lipogenic enzymes. The mTORC1 complex regulates lipid synthesis (20) through SREBP by multiple mechanisms. In response to cellular signaling, mTORC1 regulates SREBP processing through S6K and increases SREBP nuclear accumulation through Lipin 1, a phosphatidic acid phosphatase that is also a transcriptional coactivator (21–25). mTORC1 phosphorylates Lipin1, preventing its translocation into the nucleus where it can inhibit SREBP1/2-dependent transcription (24). mTORC1 also increases the activity and expression of peroxisome proliferator-activated receptor γ (PPARγ), another transcriptional regulator of lipogenic genes (26, 27). By these mechanisms, mTORC1 increases the transcription of lipogenic genes, including key enzymes in fatty acid synthesis, such as acetyl CoA carboxylase (ACC), ATP citrate lyase (ACLY), and fatty acid synthase (FASN). As we shall discuss, we have shown Lipin1 and each of these enzymes involved in fatty acid synthesis to be transcriptionally regulated by Brahma-related gene 1 (BRG1), a chromatin remodeling enzyme (28).
