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dc.contributor.authorBortell, Rita
dc.contributor.authorOwen, T. A.
dc.contributor.authorShalhoub, Victoria
dc.contributor.authorHeinrichs, A
dc.contributor.authorAronow, Michael A.
dc.contributor.authorRochette-Egly, C
dc.contributor.authorLutz, Y
dc.contributor.authorStein, Janet L.
dc.contributor.authorLian, Jane B.
dc.contributor.authorStein, Gary S.
dc.date2022-08-11T08:09:36.000
dc.date.accessioned2022-08-23T16:37:19Z
dc.date.available2022-08-23T16:37:19Z
dc.date.issued1993-03-15
dc.date.submitted2009-04-02
dc.identifier.citation<p>Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2300-4.</p>
dc.identifier.issn0027-8424 (Print)
dc.identifier.pmid8460137
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38989
dc.description.abstractThe bone-specific osteocalcin (OC) gene is transcribed only after completion of proliferation in normal diploid calvarial-derived osteoblasts during extracellular matrix mineralization. In contrast, the OC gene is expressed constitutively in both proliferating and nonproliferating ROS 17/2.8 osteosarcoma cells. To address molecular mechanisms associated with these tumor-related modifications in transcriptional control, we examined sequence-specific interactions of transactivation factors at key basal and hormone-responsive elements in the OC gene promoter. In ROS 17/2.8 cells compared to normal diploid osteoblasts, the absence of a stringent requirement for cessation of proliferation to support both induction of OC transcription and steroid hormone-mediated transcriptional modulation is reflected by modifications in transcription factor binding at (i) the two primary basal regulatory elements, the OC box (which contains a CCAAT motif as a central core) and the TATA/glucocorticoid-responsive element domain, and (ii) the vitamin D-responsive element. Particularly striking are two forms of the vitamin D receptor complex that are present in proliferating osteoblasts and osteosarcoma cells. Both forms of the complex are sensitive to vitamin D receptor antibody and retinoic X receptor antibody. After the down-regulation of proliferation, only the lower molecular weight complex is found in normal diploid osteoblasts. Both forms of the complex are present in nonproliferating ROS 17/2.8 cells with increased representation of the complex exhibiting reduced electrophoretic mobility that is phosphorylation-dependent.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=8460137&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC46074/
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectBinding Sites
dc.subjectCalcitriol
dc.subjectCell Differentiation
dc.subjectCell Division
dc.subjectDNA-Binding Proteins
dc.subjectDexamethasone
dc.subjectFetus
dc.subjectGene Expression
dc.subjectHistones
dc.subjectMolecular Sequence Data
dc.subjectNuclear Proteins
dc.subjectOligodeoxyribonucleotides
dc.subjectOsteoblasts
dc.subjectOsteocalcin
dc.subjectOsteosarcoma
dc.subject*Promoter Regions (Genetics)
dc.subjectRNA, Messenger
dc.subjectRats
dc.subject*Regulatory Sequences, Nucleic Acid
dc.subject*TATA Box
dc.subject*Transcription, Genetic
dc.subjectTumor Cells, Cultured
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleConstitutive transcription of the osteocalcin gene in osteosarcoma cells is reflected by altered protein-DNA interactions at promoter regulatory elements
dc.typeArticle
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume90
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1816
dc.identifier.contextkey808582
html.description.abstract<p>The bone-specific osteocalcin (OC) gene is transcribed only after completion of proliferation in normal diploid calvarial-derived osteoblasts during extracellular matrix mineralization. In contrast, the OC gene is expressed constitutively in both proliferating and nonproliferating ROS 17/2.8 osteosarcoma cells. To address molecular mechanisms associated with these tumor-related modifications in transcriptional control, we examined sequence-specific interactions of transactivation factors at key basal and hormone-responsive elements in the OC gene promoter. In ROS 17/2.8 cells compared to normal diploid osteoblasts, the absence of a stringent requirement for cessation of proliferation to support both induction of OC transcription and steroid hormone-mediated transcriptional modulation is reflected by modifications in transcription factor binding at (i) the two primary basal regulatory elements, the OC box (which contains a CCAAT motif as a central core) and the TATA/glucocorticoid-responsive element domain, and (ii) the vitamin D-responsive element. Particularly striking are two forms of the vitamin D receptor complex that are present in proliferating osteoblasts and osteosarcoma cells. Both forms of the complex are sensitive to vitamin D receptor antibody and retinoic X receptor antibody. After the down-regulation of proliferation, only the lower molecular weight complex is found in normal diploid osteoblasts. Both forms of the complex are present in nonproliferating ROS 17/2.8 cells with increased representation of the complex exhibiting reduced electrophoretic mobility that is phosphorylation-dependent.</p>
dc.identifier.submissionpathoapubs/1816
dc.contributor.departmentDepartment of Medicine, Division of Diabetes
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages2300-4


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