Promoter of mDMAHP/Six5: differential utilization of multiple transcription initiation sites and positive/negative regulatory elements

Hum Mol Genet. 1998 Dec;7(13):2103-12. doi: 10.1093/hmg/7.13.2103.

Abstract

We analyzed the expression of mouse DMAHP / Six5 (the myotonic dystrophy-associated homeodomain protein gene) during embryogenesis and in various tissues by northern blotting. Expression was observed as early as embryonic day 7 (E7) and continued to E17. Abundant expression was observed in neonatal heart and skeletal muscle with potential links to the phenotype of myotonic dystrophy. The transcription initiation sites of the gene were analyzed in mouse E11 and E15 embryos and in adult skeletal and heart muscle. Three major transcription initiation sites were identified, the proximal site was specific to the early E11 embryo, while the other two were common among the heart and skeletal muscle and E11 and E15 embryos. All transcription initiation sites were downstream of the corresponding CTG repeat locus of the mouse gene (-1195), excluding a possible inclusion of the CUG repeat sequence in mRNA leading to abnormal splicing or to translation of aberrant protein. For analysis of the regulatory elements in the promoter region, we used P19 embryonal carcinoma cells which abundantly express mouse DMAHP / Six5. Multiple positive and negative elements were identified in the promoter region. All positive elements were Sp1/Sp3 binding sites and one of the negative elements was a novel factor binding site. The transcription initiation sites and regulatory elements are conserved between human and mouse DMAHP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Blotting, Northern
  • Embryo, Mammalian / metabolism
  • Embryonic and Fetal Development
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Reporter / genetics
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • Molecular Sequence Data
  • Muscular Dystrophies / genetics*
  • Mutation
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Regulatory Sequences, Nucleic Acid / genetics
  • Regulatory Sequences, Nucleic Acid / physiology
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / metabolism

Substances

  • Homeodomain Proteins
  • RNA, Messenger
  • Six5 protein, mouse
  • Transcription Factors
  • Luciferases