Treatment of the hepatoma cell line HepG2 with all-trans retinoc acid (RA) induced expression of both mRNA and protein of fatty acid synthase (FAS) and SREBP-1c, an important transcriptional activator for FAS. Transient transfection of HepG2 showed that the rat FAS and murine SREBP-1c promoters responded positively to 9 cis-RA and all-trans RA. Cotransfection experiments using a human expression vector for retinoid-X receptor α identified two cis-elements essential for the RA response of the FAS promoter: the NF-Y-binding CAAT-box at -100 and the SREBP/USF-binding element at –65, known to be involved in glucose/insulin and sterol regulation. A LXR/RXR heterodimer binding site (LXRE at -660) reported to be essential for FAS regulation during lipogenesis contributed marginally to the RA-dependent upregulation of the FAS promoter. However, the LXR/RXR heterodimer binding site at -234 (Yoshikawa T. et al., 2001) conferred the full RA response on the SREBP-1c promoter in HepG2. Our data clearly demonstrate the existence of functional differences in LXREs which may well imply different roles in vivo.
|Title of host publication||Proceedings of The Physiological Society|
|Subtitle of host publication||Life Sciences 2007|
|Publisher||The Physiological Society|
|Publication status||Published - 2007|