Synergistic role of specificity proteins and upstream stimulatory factor 1 in transactivation of the mouse carboxylesterase 2/microsomal acylcarnitine hydrolase gene promoter

• Published in: Biochemical journal Vol. 384; no. Pt 1; pp. 101 - 110
• Main Authors: Furihata, Tomomi, Hosokawa, Masakiyo, Satoh, Tetsuo, Chiba, Kan
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd 15.11.2004
• Subjects: 5' Flanking Region - genetics; Animals; Carboxylic Ester Hydrolases - genetics; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Line; Cell Line, Tumor; Chlorocebus aethiops; COS Cells - chemistry; COS Cells - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Drosophila - cytology; Drosophila - genetics; E-Box Elements - genetics; Enhancer Elements, Genetic - genetics; GC Rich Sequence - genetics; Gene Expression Profiling - methods; Gene Expression Regulation, Enzymologic - genetics; Liver Neoplasms, Experimental - genetics; Liver Neoplasms, Experimental - pathology; Male; Mice; Mice, Inbred C57BL; Microsomes - enzymology; Molecular Sequence Data; NF-kappa B - genetics; Nuclear Proteins - metabolism; Organ Specificity - genetics; Promoter Regions, Genetic - genetics; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Sp1 Transcription Factor - genetics; Sp3 Transcription Factor; Transcription Factors - genetics; Transcription Factors - physiology; Transcription Initiation Site; Transcriptional Activation - genetics; Upstream Stimulatory Factors
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj20040765

Mouse carboxylesterase 2 (mCES2), a microsomal acylcarnitine hydrolase, is thought to play some important roles in fatty acid (ester) metabolism, and it is therefore thought that the level of transcription of the mCES2 gene is under tight control. Examination of the tissue expression profiles revealed that mCES2 is expressed in the liver, kidney, small intestine, brain, thymus, lung, adipose tissue and testis. When the mCES2 promoter was cloned and characterized, it was revealed that Sp1 (specificity protein 1) and Sp3 could bind to a GC box, that USF (upstream stimulatory factor) 1 could bind to an E (enhancer) box, and that Sp1 could bind to an NFkappaB (nuclear factor kappaB) element in the mCES2 promoter. Co-transfection assays showed that all of these transcription factors contributed synergistically to transactivation of the mCES2 promoter. Taken together, our results indicate that Sp1, Sp3 and USF1 are indispensable factors for transactivation of the mCES2 gene promoter. To our knowledge, this is the first study in which transcription factors that interact with a CES2 family gene have been identified. The results of the present study have provided some clues for understanding the molecular mechanisms regulating mCES2 gene expression, and should be useful for studies aimed at elucidation of physiological functions of mCES2.