Molecular cloning and characterization of the promoter region of the human Phox2b gene

Seok Jong Hong, Han Chae, Kwang Soo Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The closely related homeodomain transcription factors, Phox2a and Phox2b, are restrictively expressed in central and peripheral noradrenergic (NA) neurons in an overlapping but distinct manner, and critically regulate the differentiation and neurotransmitter identity of NA neurons. The structure and function of the human Phox2a (hPhox2a) promoter has recently been reported. Towards the long-term goal of delineating the regulatory cascade of NA neuron differentiation, we isolated a human Phox2b (hPhox2b) genomic clone encompassing approximately 7.8 kb of the 5′ upstream promoter region, the entire exon-intron structure and 4.5 kb of the 3′ flanking region. Two transcription start sites are identified to reside 115 and 110 nucleotides upstream of the start codon, based on both primer extension and 5′-rapid amplification of the cDNA ends analyses. In addition, transient transfection assays indicate that 1.1 kb or longer upstream sequences of the hPhox2b gene may confer cell type-specific gene expression in certain, but not all cell lines. The promoter activity of the hPhox2b gene is modestly transactivated by forced co-expression of Phox2b and the hPhox2b gene promoter contains a high-affinity binding site at -320 to -295 bp. This study provides a frame to further elucidate the molecular mechanisms underlying the regulation of Phox2a and Phox2b gene expression and its relation to NA differentiation.

Original languageEnglish (US)
Pages (from-to)29-39
Number of pages11
JournalMolecular Brain Research
Volume125
Issue number1-2
DOIs
StatePublished - Jun 18 2004

Keywords

  • Cell type-specific transcription
  • Cellular and molecular biology
  • Gene structure and function: general
  • Neurotransmitter identity
  • Noradrenergic neuron
  • Phox2a
  • Phox2b
  • Promoter
  • Transcription start site

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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