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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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. |
doi_str_mv | 10.1016/j.yexcr.2004.12.012 |
format | Article |
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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.</description><identifier>ISSN: 0014-4827</identifier><identifier>EISSN: 1090-2422</identifier><identifier>DOI: 10.1016/j.yexcr.2004.12.012</identifier><identifier>PMID: 15777797</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>Experimental cell research, 2005-04, Vol.305 (1), p.166-178</ispartof><rights>2004 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-dd6d3ccd2a2ff68970b99023352685c9b6da180ec49561c344bf1497ea5eb843</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.yexcr.2004.12.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15777797$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/20717583$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>D'Andrea, Barbara</creatorcontrib><creatorcontrib>Di Palma, Tina</creatorcontrib><creatorcontrib>Mascia, Anna</creatorcontrib><creatorcontrib>Motti, Maria Letizia</creatorcontrib><creatorcontrib>Viglietto, Giuseppe</creatorcontrib><creatorcontrib>Nitsch, Lucio</creatorcontrib><creatorcontrib>Zannini, Mariastella</creatorcontrib><title>The transcriptional repressor DREAM is involved in thyroid gene expression</title><title>Experimental cell research</title><addtitle>Exp Cell Res</addtitle><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.</description><subject>5' Untranslated Regions - genetics</subject><subject>60 APPLIED LIFE SCIENCES</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Blotting, Northern</subject><subject>CALCIUM</subject><subject>Calcium - metabolism</subject><subject>CALCIUM IONS</subject><subject>Calcium-Binding Proteins - genetics</subject><subject>Calcium-Binding Proteins - physiology</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>CELL PROLIFERATION</subject><subject>DNA</subject><subject>DNA Primers</subject><subject>DREAM</subject><subject>Epithelial Cells</subject><subject>GELS</subject><subject>Gene expression</subject><subject>GENE REGULATION</subject><subject>GENES</subject><subject>Kv Channel-Interacting Proteins</subject><subject>Mutagenesis</subject><subject>Rats</subject><subject>Reference Values</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - physiology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>TATA Box</subject><subject>THYROID</subject><subject>THYROID CELLS</subject><subject>Thyroid Gland - cytology</subject><subject>Thyroid Gland - physiology</subject><subject>TRANSCRIPTION</subject><subject>TRANSCRIPTION FACTORS</subject><subject>Transcription, Genetic</subject><subject>Transcriptional repression</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF1LwzAUhoMobk5_gSAFwbvWkzT9uvBC5vxiIsjuQ5ucuoyumUk3tn9vug28M7lILp73nJeHkGsKEQWa3i-iHW6ljRgAjyiLgLITMqRQQMg4Y6dkCEB5yHOWDciFcwsAyHOanpMBTTJ_imxI3mdzDDpbtk5aveq0acsmsLiy6JyxwdPX5PEj0C7Q7cY0G1T-E3TznTVaBd_YYoDbPeuDl-SsLhuHV8d3RGbPk9n4NZx-vryNH6eh9FW6UKlUxVIqVrK6TvMig6oogMVxwtI8kUWVqpLmgJIXSUplzHlVU15kWCZY5TwekdvDWOM6LZzUHcq5NG2LshMMMpoleeypuwO1suZnja4TS-0kNk3Zolk74Sl_s8SD8QGU1jhnsRYrq5el3QkKovcsFmLvWfSeBWXCe_apm-P4dbVE9Zc5ivXAwwFAb2Kj0fZNsZWotO2LKqP_XfALDbKPVw</recordid><startdate>20050415</startdate><enddate>20050415</enddate><creator>D'Andrea, Barbara</creator><creator>Di Palma, Tina</creator><creator>Mascia, Anna</creator><creator>Motti, Maria Letizia</creator><creator>Viglietto, Giuseppe</creator><creator>Nitsch, Lucio</creator><creator>Zannini, Mariastella</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TM</scope><scope>OTOTI</scope></search><sort><creationdate>20050415</creationdate><title>The transcriptional repressor DREAM is involved in thyroid gene expression</title><author>D'Andrea, Barbara ; Di Palma, Tina ; Mascia, Anna ; Motti, Maria Letizia ; Viglietto, Giuseppe ; Nitsch, Lucio ; Zannini, Mariastella</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-dd6d3ccd2a2ff68970b99023352685c9b6da180ec49561c344bf1497ea5eb843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>5' Untranslated Regions - genetics</topic><topic>60 APPLIED LIFE SCIENCES</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Blotting, Northern</topic><topic>CALCIUM</topic><topic>Calcium - metabolism</topic><topic>CALCIUM IONS</topic><topic>Calcium-Binding Proteins - genetics</topic><topic>Calcium-Binding Proteins - physiology</topic><topic>Cell Differentiation</topic><topic>Cell Line</topic><topic>CELL PROLIFERATION</topic><topic>DNA</topic><topic>DNA Primers</topic><topic>DREAM</topic><topic>Epithelial Cells</topic><topic>GELS</topic><topic>Gene expression</topic><topic>GENE REGULATION</topic><topic>GENES</topic><topic>Kv Channel-Interacting Proteins</topic><topic>Mutagenesis</topic><topic>Rats</topic><topic>Reference Values</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - physiology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>TATA Box</topic><topic>THYROID</topic><topic>THYROID CELLS</topic><topic>Thyroid Gland - cytology</topic><topic>Thyroid Gland - physiology</topic><topic>TRANSCRIPTION</topic><topic>TRANSCRIPTION FACTORS</topic><topic>Transcription, Genetic</topic><topic>Transcriptional repression</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>D'Andrea, Barbara</creatorcontrib><creatorcontrib>Di Palma, Tina</creatorcontrib><creatorcontrib>Mascia, Anna</creatorcontrib><creatorcontrib>Motti, Maria Letizia</creatorcontrib><creatorcontrib>Viglietto, Giuseppe</creatorcontrib><creatorcontrib>Nitsch, Lucio</creatorcontrib><creatorcontrib>Zannini, Mariastella</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>OSTI.GOV</collection><jtitle>Experimental cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>D'Andrea, Barbara</au><au>Di Palma, Tina</au><au>Mascia, Anna</au><au>Motti, Maria Letizia</au><au>Viglietto, Giuseppe</au><au>Nitsch, Lucio</au><au>Zannini, Mariastella</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The transcriptional repressor DREAM is involved in thyroid gene expression</atitle><jtitle>Experimental cell research</jtitle><addtitle>Exp Cell Res</addtitle><date>2005-04-15</date><risdate>2005</risdate><volume>305</volume><issue>1</issue><spage>166</spage><epage>178</epage><pages>166-178</pages><issn>0014-4827</issn><eissn>1090-2422</eissn><abstract>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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15777797</pmid><doi>10.1016/j.yexcr.2004.12.012</doi><tpages>13</tpages></addata></record> |
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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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