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dc.contributor.authorJeong, Jae-Hwan
dc.contributor.authorJung, Youn-Kwan
dc.contributor.authorKim, Hyo-Jin
dc.contributor.authorJin, Jung-Sook
dc.contributor.authorKim, Hyun-Nam
dc.contributor.authorKang, Sang-Min
dc.contributor.authorKim, Shin-Yoon
dc.contributor.authorVan Wijnen, Andre J.
dc.contributor.authorStein, Janet L.
dc.contributor.authorLian, Jane B.
dc.contributor.authorStein, Gary S.
dc.contributor.authorKato, Shigeaki
dc.contributor.authorChoi, Je-Yong
dc.date2022-08-11T08:10:56.000
dc.date.accessioned2022-08-23T17:25:49Z
dc.date.available2022-08-23T17:25:49Z
dc.date.issued2010-05-17
dc.date.submitted2011-01-11
dc.identifier.citationMolecular and Cellular Biology. 2010 May;30(10):2365-75. Epub 2010 Mar 15. <a href="http://dx.doi.org/10.1128/MCB.00672-09">Link to article on publisher's site</a>
dc.identifier.issn0270-7306 (Linking)
dc.identifier.doi10.1128/MCB.00672-09
dc.identifier.pmid20231365
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49492
dc.description.abstractThe essential osteoblast-related transcription factor Runx2 and the female steroid hormone estrogen are known to play pivotal roles in bone homeostasis; however, the functional interaction between Runx2- and estrogen-mediated signaling in skeletal tissues is minimally understood. Here we provide evidence that aromatase (CYP19), a rate-limiting enzyme responsible for estrogen biosynthesis in mammals, is transcriptionally regulated by Runx2. Consistent with the presence of multiple Runx2 binding sites, the binding of Runx2 to the aromatase promoter was demonstrated in vitro and confirmed in vivo by chromatin immunoprecipitation assays. The bone-specific aromatase promoter is activated by Runx2, and endogenous aromatase gene expression is upregulated by Runx2 overexpression, establishing the aromatase gene as a target of Runx2. The biological significance of the Runx2 transcriptional control of the aromatase gene is reflected by the enhanced estrogen biosynthesis in response to Runx2 in cultured cells. Reduced in vivo expression of skeletal aromatase gene and low bone mineral density are evident in Runx2 mutant mice. Collectively, these findings uncover a novel link between Runx2-mediated osteoblastogenic processes and the osteoblast-mediated biosynthesis of estrogen as an osteoprotective steroid hormone.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=20231365&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectAnimals
dc.subjectAromatase
dc.subjectBase Sequence
dc.subjectBone Density
dc.subjectBone and Bones
dc.subjectCell Line
dc.subjectCore Binding Factor Alpha 1 Subunit
dc.subjectEmbryo, Mammalian
dc.subjectEstrogens
dc.subjectExons
dc.subjectFemale
dc.subject*Gene Expression Regulation, Enzymologic
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMolecular Sequence Data
dc.subjectOsteoblasts
dc.subjectProgesterone
dc.subjectPromoter Regions, Genetic
dc.subjectCell Biology
dc.titleThe gene for aromatase, a rate-limiting enzyme for local estrogen biosynthesis, is a downstream target gene of Runx2 in skeletal tissues
dc.typeJournal Article
dc.source.journaltitleMolecular and cellular biology
dc.source.volume30
dc.source.issue10
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1014&amp;context=stein&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/15
dc.identifier.contextkey1724055
refterms.dateFOA2022-08-23T17:25:49Z
html.description.abstract<p>The essential osteoblast-related transcription factor Runx2 and the female steroid hormone estrogen are known to play pivotal roles in bone homeostasis; however, the functional interaction between Runx2- and estrogen-mediated signaling in skeletal tissues is minimally understood. Here we provide evidence that aromatase (CYP19), a rate-limiting enzyme responsible for estrogen biosynthesis in mammals, is transcriptionally regulated by Runx2. Consistent with the presence of multiple Runx2 binding sites, the binding of Runx2 to the aromatase promoter was demonstrated in vitro and confirmed in vivo by chromatin immunoprecipitation assays. The bone-specific aromatase promoter is activated by Runx2, and endogenous aromatase gene expression is upregulated by Runx2 overexpression, establishing the aromatase gene as a target of Runx2. The biological significance of the Runx2 transcriptional control of the aromatase gene is reflected by the enhanced estrogen biosynthesis in response to Runx2 in cultured cells. Reduced in vivo expression of skeletal aromatase gene and low bone mineral density are evident in Runx2 mutant mice. Collectively, these findings uncover a novel link between Runx2-mediated osteoblastogenic processes and the osteoblast-mediated biosynthesis of estrogen as an osteoprotective steroid hormone.</p>
dc.identifier.submissionpathstein/15
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages2365-75


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