Gene expression of the POU factor Brn-3a is regulated by two different promoters

Biochim Biophys Acta. 2002 Dec 12;1579(2-3):207-13. doi: 10.1016/s0167-4781(02)00540-7.

Abstract

Expression of the POU transcription factor Brn-3a is regulated spatially and temporally during embryogenesis and can be detected in a particular subset of neurons and neuronal tumors. In the present study, we investigated the transcriptional regulation of Brn-3a expression. The human promoter is TATA-less and contains two bona fide mRNA start sites spread over 500 nucleotides 5' of the ATG translation initiation codon. Furthermore, a second TATA-less promoter was detected in the first intron of the Brn-3a gene and our data suggest that this promoter regulates expression of the shorter isoform of the Brn-3a gene. Transcriptional activity from this promoter was found in neuronal cell lines but not in epithelial cells. The activity of this promoter was strongly enhanced upon deletion of a 24 base pair (bp) DNA element downstream of the transcription initiation sites. In addition, this DNA element was able to repress transcription from a heterologous promoter suggesting a function as a transcriptional silencer. The more distal upstream Brn-3a promoter directing the expression of the longer Brn-3a isoform is not affected by the presence of this putative 24 bp DNA element. We propose therefore that the existence of two promoters in the Brn-3a gene offers a possibility for the observed differential and cell type-specific expression of the gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • DNA-Binding Proteins / genetics*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation*
  • Humans
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Protein Isoforms / genetics
  • RNA, Messenger / genetics
  • Silencer Elements, Transcriptional
  • Transcription Factor Brn-3A
  • Transcription Factors / genetics*
  • Transcription Initiation Site
  • Transfection

Substances

  • DNA-Binding Proteins
  • POU4F1 protein, human
  • Protein Isoforms
  • RNA, Messenger
  • Transcription Factor Brn-3A
  • Transcription Factors