Detection and functional analysis of an SNP in the promoter of the human ferritin H gene that modulates the gene expression

Gene. 2006 Aug 1:377:1-5. doi: 10.1016/j.gene.2006.02.034. Epub 2006 May 5.

Abstract

The H ferritin promoter spans approximately 150 bp, upstream of the transcription start and is composed by two cis-elements in position -132 (A box) and -62 (B-box), respectively. The A box is recognized by the transcription factor Sp1, and the B-box by a protein complex called Bbf, which includes the CAAT binding factor NF-Y. In this study we performed a functional analysis of an H ferritin promoter allele carrying a G to T substitution adjacent to the Bbf binding site, in position -69. In vitro studies with reporter constructs revealed a significantly reduced transcriptional activity of this allele compared to that of the w.t. promoter that was mirrored by a decrease in Bbf binding. In vivo, this variant genotype is accompanied by a reduced amount of the H mRNA in peripheral blood lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Binding Sites / genetics
  • CCAAT-Binding Factor / metabolism
  • DNA / genetics
  • DNA / metabolism
  • Ferritins / genetics*
  • Gene Expression
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sp1 Transcription Factor / metabolism
  • Transcription, Genetic

Substances

  • CCAAT-Binding Factor
  • RNA, Messenger
  • Sp1 Transcription Factor
  • DNA
  • Ferritins