LAP (NF-IL6) TRANSACTIVATES THE COLLAGEN-ALPHA(1)(I) GENE FROM A 5' REGULATORY REGION

Although collagen is known to enhance hepatocyte differentiation and hepatocytes produce collagen in vivo, the transcriptional factors responsible for collagen type I gene expression in hepatic cells are not known. LAP (Liver Activator Protein) is a member of the C/EBP family, which in differentiated hepatocytes contributes to the high levels of liver-specific gene expression. In this study we show that LAP binds to the collagen cr,(T) promoter at bath reverse CCAAT motifs and activates transcription. Furthermore, an upstream element, collagen element I(-370/-344), which shares homology with the LAP binding cis-element of the albumin promoter (9 of 13 bp) is described. This collagen element I stimulates transcription in both orientations and when placed in front of either a homologous or a heterologous chimeric report construct. These experiments suggest that LBP may be important in the expression of collagen in differentiated hepatocytes through both the promoter and a newly described upstream element.