Role of TG-interacting factor (Tgif) in lipid metabolism

• Tgif1 and Tgif2 may repress several transcriptional pathways activated by lipids.
• Tgif1 can interact with LXRα to repress transcription in vitro and in vivo.
• Tgif1 acts as a transcriptional repressor of the cholesterol esterifying enzyme Acat2.
• No studies have yet been published investigating the role of Tgif2 in lipid metabolism.
• Lipid analyses in subjects with mutations in these genes are still lacking.

TG interacting factors (Tgifs) 1 and 2 are members of the TALE (three-amino-acid loop extension) superfamily of homeodomain proteins. These two proteins bind to the same DNA sequence and share a conserved C-terminal repression domain. Mutations in TGIF1 have been linked to holoprosencephaly, which is a human genetic disease that affects craniofacial development. As these proteins can interact with the ligand binding domain of retinoid X receptor α, a common heterodimeric partner of several nuclear receptors [e.g., liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs)], Tgif1 and Tgif2 might repress other transcriptional pathways activated by lipids. In line with this, Tgif1 interacts with LXRα and Tgif1 null mice have increased expression of the two Lxrα target genes apolipoproteins (Apo) c2 and a4. Also, we have recently identified Tgif1 to function as a transcriptional repressor of the cholesterol esterifying enzyme acyl-coenzyme A:cholesterol acyltransferase 2 (gene name SOAT2). As no studies yet have shown involvement of Tgif2 in the lipid metabolism, this review will focus on the role of Tgif1 in lipid and cholesterol metabolism. This article is part of a Special Issue entitled: Linking transcription to physiology in lipodomics.