SND p102 is a rat liver endoplasmic reticulum cholesterol ester hydrolase recently described as a member of a conserved family of transcriptional coactivators that promotes phospholipid secretion into lipoproteins when overexpressed in hepatocytes. In this work, we report first evidence for a mechanism of transcriptional regulation for the SND p102 (Snd1) gene. Promoter activity of 5' deletion fragments determined in human HepG2 and rat McA-RH7777 hepatoma cells by luciferase reporter gene assays showed a minimal promoter involving two inverted CCAAT boxes. EMSA demonstrated specific binding of Sp1 to GC boxes in the proximal, highly active promoter region besides that of NF-Y to CCAAT boxes reported earlier. Site-directed disruption of such CCAAT and GC boxes led to reduction in transcriptional activity, confirming the functional implication of NF-Y and Sp1 in SND p102 gene transcription. (c) 2007 Elsevier Inc. All rights reserved.