Structure, upstream promoter region, and functional domains of a mouse and human Mix paired-like homeobox gene

Kenneth Sahr, Dora Campos Dias, Roberto Sanchez, Dongli Chen, Siming W. Chen, Lorraine J. Gudas, Margaret H. Baron

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Mix/Bix proteins represent a vertebrate subgroup of paired-like homeodomain proteins which are known to function around the time of gastrulation. Here we report the structures of the genomic and upstream promoter regions of a mouse and human Mix-like gene. Both genes map to syntenic regions of chromosome 1 and contain two coding exons, with the paired-type homeodomain split between the exons within helix 3. Differentiating mouse embryonic stem cells transcribe a messenger RNA of ∼2.6 kb. The first exon encodes the translation initiation codon and a 5′ untranslated region of ∼90 bp. Sequence analysis of the 960 bp upstream of the transcription start site of the mouse Mix gene revealed the presence of a putative initiator region and TATA box as well as potential Smad, FoxH1/FAST, T-box, COUP-TF, C/EBP, GATA, HNF3 binding sites and retinoic acid response elements. A number of these sites are conserved in the human Mix promoter. We find that most paired-related homeodomain proteins, including mouse and human Mix, contain a proline-rich region within their amino termini which may interact with other proteins. Mouse and human Mix proteins contain highly conserved carboxy-terminal polar/acidic regions with the potential to form an amphipathic helix and the ability to activate transcription in yeast. Mouse Mix expressed in COS cells or in vitro binds a DNA consensus sequence identified previously for paired class homeodomain proteins. These studies suggest that a number of features of paired-like protein structure and function are conserved across diverse species and provide a useful framework for studying the function and regulation of the mouse Mix gene.

Original languageEnglish
Pages (from-to)135-147
Number of pages13
JournalGene
Volume291
Issue number1-2
DOIs
StatePublished - 29 May 2002

Keywords

  • Endoderm
  • Gastrulation
  • Homeodomain
  • Mesoderm
  • Transcription factor

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