Analysis of the promoter region of human placenta-specific DSCR4 gene

Biochim Biophys Acta. 2008 Jan;1779(1):40-50. doi: 10.1016/j.bbagrm.2007.09.005. Epub 2007 Dec 4.

Abstract

The gene DSCR4 locates in the band q22.2 of human chromosome 21 and encodes a protein of 118 amino acids. Expression of DSCR4 is restricted to human placenta and placental choriocarcinoma cell lines BeWo and JEG3. The 5'-RACE method using RNA from human placenta indicated the major transcription start site at 93 nt upstream (nt -93) of the initiation codon. Transfection assay using a series of deletion constructs of the 5'-flanking region fused to the luciferase reporter gene identified three positive regions nt -2200 to -2088, nt -2064 to -1924, nt -810 to -632 and two negative regions nt -1923 to -1740, nt -631 to -425. The computer analysis predicted the presence of several cis-elements in these regions and the promoter assay using various mutants of consensus sequence identified two distinct cis-elements for OLF-1 and E47. The electrophoretic mobility shift assay (EMSA) using the extracts of DSCR4-expressing cells confirmed the binding of certain protein factors to these cis-elements. In fact, OLF-1-like transcription factor, EBF-3 and EBF-4 were detected in the DSCR4-expressing cell lines and human placenta. Based on these data, we postulated that transcription of DSCR4 gene is regulated positively by binding of OLF-1-like transcription factor and negatively by binding of E47-like transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Flanking Region
  • Base Sequence
  • Binding Sites / genetics
  • Cell Line
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Electrophoretic Mobility Shift Assay
  • Female
  • Gene Expression
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy Proteins / genetics*
  • Promoter Regions, Genetic*
  • RNA, Long Noncoding
  • TCF Transcription Factors / metabolism
  • Tissue Distribution
  • Trans-Activators / metabolism
  • Transcription Factor 7-Like 1 Protein
  • Transcription, Genetic

Substances

  • DNA-Binding Proteins
  • DSCR4 lncRNA, human
  • EBF1 protein, human
  • Pregnancy Proteins
  • RNA, Long Noncoding
  • TCF Transcription Factors
  • TCF7L1 protein, human
  • Trans-Activators
  • Transcription Factor 7-Like 1 Protein
  • DNA