Organization of human ACAT-2 gene and its cell-type-specific promoter activity

Acyl-CoA:cholesterol acyltransferase (ACAT) plays important roles in cellul ar cholesterol homeostasis. Two ACAT genes exist in mammals. We report here the genomic organization of human ACAT-2 gene and analysis of its promoter activity in various cell lines. The human ACAT-2 gene spans over 18 kb and contains 15 exons, Three transcription start sites and one poly(A) site ar e identified by the 5'/3'-RACE. In addition, the human ACAT-2 gene is linke d to the insulinlike growth factor binding protein 6 (IGFBP-6) gene in a he ad-to tail manner with a small intergenic region of about 1.2 kb. The 5'-fl anking region of human ACAT-2 gene contains many potential cis-acting eleme nts for multiple transcriptional regulatory factors but lacks TATA and CCAA T boxes. Using promoter-luciferase reporter assays, we demonstrate the tran scriptional activity of ACAT-2 gene promoter is high in Caco-2 cells, espec ially after these cells become postconfluent and behave as intestinal enter ocytes. (C) 2001 Academic Press.