The transcriptional repressor DREAM is involved in thyroid gene expression

Downstream regulatory element antagonistic modulator (DREAM) was originally identified in neuroendocrine cells as a calcium-binding protein that specifically binds to downstream regulatory elements (DRE) on DNA, and represses transcription of its target genes. To explore the possibility that DREAM m...

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Veröffentlicht in:Experimental cell research 2005-04, Vol.305 (1), p.166-178
Hauptverfasser: D'Andrea, Barbara, Di Palma, Tina, Mascia, Anna, Motti, Maria Letizia, Viglietto, Giuseppe, Nitsch, Lucio, Zannini, Mariastella
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container_end_page 178
container_issue 1
container_start_page 166
container_title Experimental cell research
container_volume 305
creator D'Andrea, Barbara
Di Palma, Tina
Mascia, Anna
Motti, Maria Letizia
Viglietto, Giuseppe
Nitsch, Lucio
Zannini, Mariastella
description Downstream regulatory element antagonistic modulator (DREAM) was originally identified in neuroendocrine cells as a calcium-binding protein that specifically binds to downstream regulatory elements (DRE) on DNA, and represses transcription of its target genes. To explore the possibility that DREAM may regulate the endocrine activity of the thyroid gland, we analyzed its mRNA expression in undifferentiated and differentiated thyroid cells. We demonstrated that DREAM is expressed in the normal thyroid tissue as well as in differentiated thyroid cells in culture while it is absent in FRT poorly differentiated cells. In the present work, we also show that DREAM specifically binds to DRE sites identified in the 5′ untranslated region (UTR) of the thyroid-specific transcription factors Pax8 and TTF-2/FoxE1 in a calcium-dependent manner. By gel retardation assays we demonstrated that thapsigargin treatment increases the binding of DREAM to the DRE sequences present in Pax8 and TTF-2/Foxe1 5′ UTRs, and this correlates with a significant reduction of the expression of these genes. Interestingly, in poorly differentiated thyroid cells overexpression of exogenous DREAM strongly inhibits Pax8 expression. Moreover, we provide evidence that a mutated form of DREAM unable to bind Ca 2+ interferes with thyroid cell proliferation. Therefore, we propose that in thyroid cells DREAM is a mediator of the calcium-signaling pathway and it is involved in the regulation of thyroid cell function.
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1090-2422
language eng
recordid cdi_osti_scitechconnect_20717583
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subjects 5' Untranslated Regions - genetics
60 APPLIED LIFE SCIENCES
Animals
Base Sequence
Blotting, Northern
CALCIUM
Calcium - metabolism
CALCIUM IONS
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - physiology
Cell Differentiation
Cell Line
CELL PROLIFERATION
DNA
DNA Primers
DREAM
Epithelial Cells
GELS
Gene expression
GENE REGULATION
GENES
Kv Channel-Interacting Proteins
Mutagenesis
Rats
Reference Values
Repressor Proteins - genetics
Repressor Proteins - physiology
Reverse Transcriptase Polymerase Chain Reaction
TATA Box
THYROID
THYROID CELLS
Thyroid Gland - cytology
Thyroid Gland - physiology
TRANSCRIPTION
TRANSCRIPTION FACTORS
Transcription, Genetic
Transcriptional repression
title The transcriptional repressor DREAM is involved in thyroid gene expression
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