First Author | Smit JJ | Year | 1995 |
Journal | Biochim Biophys Acta | Volume | 1261 |
Issue | 1 | Pages | 44-56 |
PubMed ID | 7893760 | Mgi Jnum | J:23740 |
Mgi Id | MGI:71431 | Doi | 10.1016/0167-4781(94)00214-n |
Citation | Smit JJ, et al. (1995) Characterization of the promoter region of the human MDR3 P-glycoprotein gene. Biochim Biophys Acta 1261(1):44-56 |
abstractText | The human MDR3 (or MDR2) P-glycoprotein is probably involved in the transport of phospholipids from liver hepatocytes into bile (Smit et al. (1993) Cell 75, 451-462). In accordance with this function, MDR3 is highly expressed in human liver, but lower mRNA levels were also found in adrenal, heart, muscle and cells of the B-cell compartment. We have cloned and analyzed the MDR3 promoter region. It is GC-rich, and contains neither a TATA nor a CAAT box, but it does contain multiple putative SP1 binding sites, features also found in so-called housekeeping genes. RNase protection and primer extension analyses indicate that the MDR3 gene has multiple transcription start sites in a GC-rich region with considerable homology to the putative mouse mdr2 promoter. A 3 kb genomic fragment containing the MDR3 start sites directs transcription of a chloramphenicol acetyltransferase (CAT) reporter gene upon transient transfection in the human hepatoma cell line HepG2. This transcription is orientation dependent, and stimulated by a SV40 enhancer, indicating that the 3 kb insert contains the core promoter elements of the MDR3 gene. The promoter region contains several consensus sequences where known or putative liver-specific (C/EBP, HNF5) or lymphoid specific (Pu.1, ets-1) transcription factors may bind. |