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dc.contributor.authorvan Gurp, Maria F.
dc.contributor.authorPratap, Jitesh
dc.contributor.authorLuong, Mai X.
dc.contributor.authorJaved, Amjad
dc.contributor.authorHoffmann, Heidi M.
dc.contributor.authorGiordano, Antonio
dc.contributor.authorStein, Janet L.
dc.contributor.authorNeufeld, Ellis J.
dc.contributor.authorLian, Jane B.
dc.contributor.authorStein, Gary S.
dc.contributor.authorVan Wijnen, Andre J.
dc.date2022-08-11T08:09:51.000
dc.date.accessioned2022-08-23T16:46:18Z
dc.date.available2022-08-23T16:46:18Z
dc.date.issued1999-12-22
dc.date.submitted2008-06-18
dc.identifier.citationCancer Res. 1999 Dec 1;59(23):5980-8.
dc.identifier.issn0008-5472 (Print)
dc.identifier.pmid10606245
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40854
dc.description.abstractDevelopmental control of bone tissue-specific genes requires positive and negative regulatory factors to accommodate physiological requirements for the expression or suppression of the encoded proteins. Osteocalcin (OC) gene transcription is restricted to the late stages of osteoblast differentiation. OC gene expression is suppressed in nonosseous cells and osteoprogenitor cells and during the early proliferative stages of bone cell differentiation. The rat OC promoter contains a homeodomain recognition motif within a highly conserved multipartite promoter element (OC box I) that contributes to tissue-specific transcription. In this study, we demonstrate that the CCAAT displacement protein (CDP), a transcription factor related to the cut homeodomain protein in Drosophila melanogaster, may regulate bone-specific gene transcription in immature proliferating osteoblasts. Using gel shift competition assays and DNase I footprinting, we show that CDP/cut recognizes two promoter elements (TATA and OC box I) of the bone-related rat OC gene. Overexpression of CDP/cut in ROS 17/2.8 osteosarcoma cells results in repression of OC promoter activity; this repression is abrogated by mutating OC box I. Gel shift immunoassays show that CDP/cut forms a proliferation-specific protein/DNA complex in conjunction with cyclin A and p107, a member of the retinoblastoma protein family of tumor suppressors. Our findings suggest that CDP/cut may represent an important component of a cell signaling mechanism that provides cross-talk between developmental and cell cycle-related transcriptional regulators to suppress bone tissue-specific genes during proliferative stages of osteoblast differentiation.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10606245&dopt=Abstract">Link to article in PubMed</a>
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectBinding Sites
dc.subjectCell Differentiation
dc.subjectCyclin A
dc.subjectDrosophila melanogaster
dc.subjectHomeodomain Proteins
dc.subjectMolecular Sequence Data
dc.subjectNuclear Proteins
dc.subjectOsteoblasts
dc.subjectOsteocalcin
dc.subjectOsteosarcoma
dc.subject*Promoter Regions (Genetics)
dc.subjectRats
dc.subjectRecombinant Fusion Proteins
dc.subjectRepressor Proteins
dc.subjectRetinoblastoma Protein
dc.subjectTATA Box
dc.subject*Transcription, Genetic
dc.subjectTransfection
dc.subjectTumor Cells, Cultured
dc.subjectCancer Biology
dc.subjectCell Biology
dc.subjectOncology
dc.titleThe CCAAT displacement protein/cut homeodomain protein represses osteocalcin gene transcription and forms complexes with the retinoblastoma protein-related protein p107 and cyclin A
dc.typeJournal Article
dc.source.journaltitleCancer research
dc.source.volume59
dc.source.issue23
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1365&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/366
dc.identifier.contextkey533076
refterms.dateFOA2022-08-23T16:46:18Z
html.description.abstract<p>Developmental control of bone tissue-specific genes requires positive and negative regulatory factors to accommodate physiological requirements for the expression or suppression of the encoded proteins. Osteocalcin (OC) gene transcription is restricted to the late stages of osteoblast differentiation. OC gene expression is suppressed in nonosseous cells and osteoprogenitor cells and during the early proliferative stages of bone cell differentiation. The rat OC promoter contains a homeodomain recognition motif within a highly conserved multipartite promoter element (OC box I) that contributes to tissue-specific transcription. In this study, we demonstrate that the CCAAT displacement protein (CDP), a transcription factor related to the cut homeodomain protein in Drosophila melanogaster, may regulate bone-specific gene transcription in immature proliferating osteoblasts. Using gel shift competition assays and DNase I footprinting, we show that CDP/cut recognizes two promoter elements (TATA and OC box I) of the bone-related rat OC gene. Overexpression of CDP/cut in ROS 17/2.8 osteosarcoma cells results in repression of OC promoter activity; this repression is abrogated by mutating OC box I. Gel shift immunoassays show that CDP/cut forms a proliferation-specific protein/DNA complex in conjunction with cyclin A and p107, a member of the retinoblastoma protein family of tumor suppressors. Our findings suggest that CDP/cut may represent an important component of a cell signaling mechanism that provides cross-talk between developmental and cell cycle-related transcriptional regulators to suppress bone tissue-specific genes during proliferative stages of osteoblast differentiation.</p>
dc.identifier.submissionpathoapubs/366
dc.contributor.departmentDepartment of Cell Biology and Cancer Center
dc.source.pages5980-8


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