Characterization of the promoter region of the human MDR3 P-glycoprotein gene

Biochim Biophys Acta. 1995 Mar 14;1261(1):44-56. doi: 10.1016/0167-4781(94)00214-n.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular / pathology
  • Cloning, Molecular
  • Consensus Sequence
  • DNA, Complementary / genetics
  • Enhancer Elements, Genetic
  • Exons / genetics
  • Gene Expression Regulation
  • Genes*
  • Genes, Reporter
  • Humans
  • Liver Neoplasms / pathology
  • Mice / genetics
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • RNA Splicing
  • Recombinant Fusion Proteins / biosynthesis
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • DNA, Complementary
  • Recombinant Fusion Proteins

Associated data

  • GENBANK/Z35284
  • GENBANK/Z35285
  • GENBANK/Z35286
  • GENBANK/Z35287