Cloning and characterization of the BRD7 gene promoter

DNA Cell Biol. 2006 Jun;25(6):346-58. doi: 10.1089/dna.2006.25.346.

Abstract

BRD7, a novel bromodomain gene, encodes a protein that inhibits cell growth and cell cycle progression by transcriptional regulation of some cell cycle-related genes. Its transcriptional down-expression has been shown to be critical to the pathogenesis of Nasopharyngeal carcinoma (NPC). Little is known about the transcriptional mechanisms controlling BRD7 gene expression. In this paper, we have characterized the 5' regulatory region of the BRD7 gene in order to understand the molecular mechanisms regulating its expression. Transient transfection results suggested that the analyzed upstream sequences of the BRD7 gene might contain some important but not sufficient sequence information to confer the cell-type specificity of BRD7 gene expression. Further analysis with a series of deletions demonstrated that a 125-bp region was required for the basal promoter activity of the BRD7 gene. Results from ChIP and EMSA indicated that the promoter was responsive to Sp1, E2F, and E2F6. All of these suggest a possible mechanism that transcriptional factor Sp1, E2F, and E2F-6 are associated in the BRD7 promoter region and regulate BRD7 promoter activity. Taken together, these results will help to better understand the role of the BRD7 gene in signal-dependent transcriptional regulation, and to develop new reagents for therapeutic upregulation of the BRD7 gene in NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cloning, Molecular
  • DNA Primers
  • Humans
  • Molecular Sequence Data
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / pathology
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic*
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sp1 Transcription Factor / metabolism

Substances

  • BRD7 protein, human
  • Chromosomal Proteins, Non-Histone
  • DNA Primers
  • Nuclear Proteins
  • Sp1 Transcription Factor