Human, bovine, canine and rat thyroglobulin promoter sequences display species-specific differences in an in vitro study

The dog thyroid primary culture system: a model of the regulation of function, growth and differentiation expression by cAMP and other well-defined signaling cascades

“…For still unknown reasons, this proved to be the right choice. Transfection of DNA constructs containing the chloramphenicol acetyltransferase reporter gene under the control of the sequences located 5 0 to the transcribed part of the Tg gene demonstrated that these DNA sequences are able to control transcription of the reporter gene in response to cAMP stimulation in the dog cells (118)(119)(120). The minimal sequences required for proper promoter activity were narrowed down by a deletion approach to about the first 200 bp preceding the transcription start of the gene.…”

“…Most of these sequences are part of the proximal hypersensitive site identified previously in Tg gene chromatin in thyroid cells (see earlier section on chromatin structure of the Tg gene). Tg promoters from different mammalian species, including dog, cattle, man and rat, are equally active when transfected into dog thyrocytes, which suggests that some basic molecular mechanisms involved in the control of Tg gene transcription have been conserved among these species (119). Mutagenesis experiments revealed that thyroid transcription factor-1 (TTF-1) (121) plays a major role in the transcriptional activity of the Tg promoter (122).…”

Thyroid transcription factor 1 and Pax8 synergistically activate the promoter of the human thyroglobulin gene

“…Generally, mutagenesis experiments at homologous positions in four Tg promoters (from cattle, rat, man and dog) indicated that, despite the overall DNA sequence conservation, the molecular mechanisms involved in the control of Tg gene expression have evolved differently within mammals (Donda et al 1991(Donda et al , 1993. In other words, the isolated changes accumulated during evolution result in different behaviors of the Tg promoters, when subjected to equivalent mutagenesis.…”

“…human gene, there is only one functional study of the human Tg promoter activity, which could be demonstrated only in the presence of forskolin (Donda et al 1993). Generally, mutagenesis experiments at homologous positions in four Tg promoters (from cattle, rat, man and dog) indicated that, despite the overall DNA sequence conservation, the molecular mechanisms involved in the control of Tg gene expression have evolved differently within mammals (Donda et al 1991(Donda et al , 1993.…”

“…Studies in these species have shown that the region up to 200 nucleotides contains all the potential regulatory elements for thyroid-specific transcription (Donda et al 1993). Although transiently transfected promoter sequences from the species indicated in the previous paragraph, when linked to reporter genes, exhibited equal activity after transfection into heterologous thyroid cells (Donda et al 1993), mutagenesis experiments at homologous positions indicated that, despite the overall DNA sequence conservation, the molecular mechanisms involved in the control of Tg gene expression have evolved differently within mammals (Donda et al 1991(Donda et al , 1993. Understanding of these mechanisms has allowed the rat Tg promoter to be used for an in vitro suicide gene/prodrug therapy in an animal model of differentiated thyroid carcinomas (Braiden et al 1998, Nagayama et al 1999.…”