{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361699994163546752.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.0902191106"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.0902191106"}},{"identifier":{"@type":"PMID","@value":"19416882"}}],"dc:title":[{"@value":"An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Regulation of age-related changes in gene expression underlies many diseases. We previously discovered the first puberty-onset gene switch, the age-related stability element (ASE)/age-related increase element (AIE)-mediated genetic mechanism for age-related gene regulation. Here, we report that this mechanism underlies the mysterious puberty-onset amelioration of abnormal bleeding seen in hemophilia B Leyden. Transgenic mice robustly mimicking the Leyden phenotype were constructed. Analysis of these animals indicated that ASE plays a central role in the puberty-onset amelioration of the disease. Human factor IX expression in these animals was reproducibly nullified by hypophysectomy, but nearly fully restored by administration of growth hormone, being consistent with the observed sex-independent recovery of factor IX expression. Ets1 was identified as the specific liver nuclear protein binding only to the functional ASE, G/CAGGAAG, and not to other Ets consensus elements. This study demonstrates the clinical relevance of the first discovered puberty-onset gene switch, the ASE/AIE-mediated regulatory mechanism.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380294741228909441","@type":"Researcher","foaf:name":[{"@value":"Sumiko Kurachi"}],"jpcoar:affiliationName":[{"@value":"Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba, 305-8566 Japan; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294741228909442","@type":"Researcher","foaf:name":[{"@value":"Jeffrey S. Huo"}],"jpcoar:affiliationName":[{"@value":"Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-5618"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294741228909444","@type":"Researcher","foaf:name":[{"@value":"Afshin Ameri"}],"jpcoar:affiliationName":[{"@value":"Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-5618"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294741228909440","@type":"Researcher","foaf:name":[{"@value":"Kezhong Zhang"}],"jpcoar:affiliationName":[{"@value":"Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-5618"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294741228909445","@type":"Researcher","foaf:name":[{"@value":"Akiyasu C. Yoshizawa"}],"jpcoar:affiliationName":[{"@value":"Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba, 305-8566 Japan; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294741228909443","@type":"Researcher","foaf:name":[{"@value":"Kotoku Kurachi"}],"jpcoar:affiliationName":[{"@value":"Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba, 305-8566 Japan; and"},{"@value":"Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-5618"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2009-05-12","prism:volume":"106","prism:number":"19","prism:startingPage":"7921","prism:endingPage":"7926"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.0902191106"}],"createdAt":"2009-04-29","modifiedAt":"2022-04-12","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Aging","dc:title":"Aging"},{"@id":"https://cir.nii.ac.jp/all?q=Time%20Factors","dc:title":"Time Factors"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Transgenic","dc:title":"Mice, Transgenic"},{"@id":"https://cir.nii.ac.jp/all?q=Hemophilia%20A","dc:title":"Hemophilia A"},{"@id":"https://cir.nii.ac.jp/all?q=Factor%20IX","dc:title":"Factor IX"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Sex%20Factors","dc:title":"Sex Factors"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20Expression%20Regulation","dc:title":"Gene Expression Regulation"},{"@id":"https://cir.nii.ac.jp/all?q=Growth%20Hormone","dc:title":"Growth Hormone"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Homeostasis","dc:title":"Homeostasis"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Female","dc:title":"Female"},{"@id":"https://cir.nii.ac.jp/all?q=Protein%20Binding","dc:title":"Protein Binding"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050001202617611264","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Development of a bioassay to screen for chemicals mimicking the anti-aging effects of calorie restriction"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004231520771200","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"First case report of hemophilia B Leyden in Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285706521996160","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Age-related expression analysis of mouse liver nuclear protein binding to 3′-untranslated region of Period2 gene"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.0902191106"},{"@type":"OPENAIRE","@value":"doi_dedup___::bb110f6e5c2187ede9f032cef81eff22"},{"@type":"CROSSREF","@value":"10.1007/s12185-017-2194-4_references_DOI_3ldh7hwvY5YKrjsou1y7qcmJnTz"},{"@type":"CROSSREF","@value":"10.1007/s12576-015-0373-8_references_DOI_3ldh7hwvY5YKrjsou1y7qcmJnTz"},{"@type":"CROSSREF","@value":"10.1016/j.bbrc.2010.09.032_references_DOI_3ldh7hwvY5YKrjsou1y7qcmJnTz"}]}