Functional analysis of the murine Pax8 promoter reveals autoregulation and the presence of a novel thyroid-specific DNA-binding activity.
BACKGROUND
Organogenesis of the thyroid gland requires the Pax8 protein. Absence or reduction of Pax8 results in congenital hypothyroidism in animal models and humans, respectively. This study aims at elucidating the regulatory mechanism leading to the expression of Pax8 in thyroid cells.


METHODS
The murine Pax8 gene promoter was functionally dissected by mutagenesis and transfection in the thyroid cell line FRTL-5. Nuclear factors important for thyroid-specific gene expression were identified by DNA-binding assays.


RESULTS
We show that Pax8 binds to and controls the expression of its own promoter. Furthermore, we identify a novel, thyroid-specific, DNA-binding activity (denominated nTTF [for novel Thyroid Transcription Factor]) that recognizes a specific region of the Pax8 promoter.


CONCLUSIONS
The Pax8 promoter appears to be autoregulated, a feature that might be responsible for the haploinsufficiency displayed by this gene.
IRGS, Biogem, Avellino, Italy.
Alessandra
A
di Gennaro
Olga
O
Spadaro
Maria Giuseppina
MG
Baratta
Mario
M
De Felice
Roberto
R
Di Lauro
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D006706:Homeostasis / Q000235:genetics*; D051379:Mice; D016296:Mutagenesis; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013961:Thyroid Gland / Q000378:metabolism*; D015533:Transcriptional Activation
D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse