TG-interacting factor 1 acts as a transcriptional repressor of sterol O-acyltransferase 2.
Acat2 [gene name: sterol O-acyltransferase 2 (SOAT2)] esterifies cholesterol in enterocytes and hepatocytes. This study aims to identify repressor elements in the human SOAT2 promoter and evaluate their in vivo relevance. We identified TG-interacting factor 1 (Tgif1) to function as an important repressor of SOAT2. Tgif1 could also block the induction of the SOAT2 promoter activity by hepatocyte nuclear factor 1α and 4α. Women have ∼ 30% higher hepatic TGIF1 mRNA compared with men. Depletion of Tgif1 in mice increased the hepatic Soat2 expression and resulted in higher hepatic lipid accumulation and plasma cholesterol levels. Tgif1 is a new player in human cholesterol metabolism.
Division of Clinical Chemistry, Department of Laboratory Medicine, and Centre for Nutrition and Toxicology, NOVUM, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Camilla
C
Pramfalk
Tiffany A
TA
Melhuish
David
D
Wotton
Zhao-Yan
ZY
Jiang
Mats
M
Eriksson
Paolo
P
Parini
D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D004794:Enzyme Repression; D005260:Female; D042882:Gallstones / Q000201:enzymology; D020868:Gene Silencing; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000502:physiology; D051557:Hepatocyte Nuclear Factor 4 / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000502:physiology*; D012727:Sex Characteristics; D002785:Sterol O-Acyltransferase / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D000097587:Sterol O-Acyltransferase 2
D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D018398:Homeodomain Proteins; D008055:Lipids; D012097:Repressor Proteins; D002785:Sterol O-Acyltransferase; D014157:Transcription Factors; D000097587:Sterol O-Acyltransferase 2; C496487:HNF1A protein, human; C496592:HNF4A protein, human; C491172:MEIS2 protein, human; C097504:TGIF1 protein, human
hepatocyte nuclear factor 1α and 4α; human; liver; triglyceride