Cooperative regulation of CYP3A5 gene transcription by NF-Y and Sp family members

Biochem Biophys Res Commun. 2001 Aug 10;286(1):55-60. doi: 10.1006/bbrc.2001.5352.


The purpose of this study was to clarify the mechanism(s) responsible for the transcriptional regulation of the human CYP3A5 gene. It was found that a region from nucleotides -90 to -40 was involved in the transcriptional activity of the CYP3A5 gene by transfection of a series of 5'-truncated promoter-luciferase chimeric genes into human hepatoma HepG2 cells. A gel shift assay using nuclear extracts prepared from HepG2 cells showed that nuclear factor-Y (NF-Y) and specificity protein (Sp) 1 and Sp3 bound to CCAAT box (-78/-68) and a basic transcription element (BTE) (-67/-46) in the CYP3A5 gene. Furthermore, introduction of mutations in the CCAAT box, the BTE, or both elements decreased the transcriptional activity to 10, 21, or 4% of that seen with the intact gene. Thus, we conclude that the transcription of the CYP3A5 gene is cooperatively regulated by NF-Y, Sp1, and Sp3 in HepG2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CCAAT-Binding Factor / physiology*
  • Cloning, Molecular
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics*
  • DNA
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Enzymologic / physiology*
  • Humans
  • Molecular Sequence Data
  • Sp1 Transcription Factor / physiology*
  • Sp3 Transcription Factor
  • Transcription Factors / physiology*
  • Transcription, Genetic / physiology*
  • Tumor Cells, Cultured


  • CCAAT-Binding Factor
  • DNA-Binding Proteins
  • SP3 protein, human
  • Sp1 Transcription Factor
  • Transcription Factors
  • Sp3 Transcription Factor
  • DNA
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A