{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Manual"},"PMID":{"@attributes":{"Version":"1"},"@text":"11172719"},"DateCompleted":{"Year":"2001","Month":"03","Day":"22"},"DateRevised":{"Year":"2026","Month":"01","Day":"28"},"Article":{"@attributes":{"PubModel":"Print"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Print"},"@text":"1097-2765"},"JournalIssue":{"@attributes":{"CitedMedium":"Print"},"Volume":"7","Issue":"1","PubDate":{"Year":"2001","Month":"Jan"}},"Title":"Molecular cell","ISOAbbreviation":"Mol Cell"},"ArticleTitle":"Two-step regulation of left-right asymmetric expression of Pitx2: initiation by nodal signaling and maintenance by Nkx2.","Pagination":{"StartPage":"137","EndPage":"149","MedlinePgn":"137-49"},"Abstract":{"AbstractText":["Pitx2 is left--right (L--R) asymmetrically expressed initially in the lateral plate and later in primordial visceral organs. The transcriptional regulatory mechanisms that underlie L--R asymmetric expression of Pitx2 were investigated. Mouse Pitx2 has a left side-specific enhancer (ASE) that mediates both the initiation and maintenance of L--R asymmetric expression. This element contains three binding sites for the transcription factor FAST. The FAST binding sites function as Nodal-responsive elements and are sufficient for the initiation but not for the maintenance of asymmetric expression. The maintenance requires an Nkx2-5 binding site also present within the ASE. These results suggest that the left-sided expression of Pitx2 is directly initiated by Nodal signaling and is subsequently maintained by Nkx2. Such two-step control may represent a general mechanism for gene regulation during development."]},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Shiratori","ForeName":"H","Initials":"H","AffiliationInfo":[{"Affiliation":"Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Sakuma","ForeName":"R","Initials":"R"},{"@attributes":{"ValidYN":"Y"},"LastName":"Watanabe","ForeName":"M","Initials":"M"},{"@attributes":{"ValidYN":"Y"},"LastName":"Hashiguchi","ForeName":"H","Initials":"H"},{"@attributes":{"ValidYN":"Y"},"LastName":"Mochida","ForeName":"K","Initials":"K"},{"@attributes":{"ValidYN":"Y"},"LastName":"Sakai","ForeName":"Y","Initials":"Y"},{"@attributes":{"ValidYN":"Y"},"LastName":"Nishino","ForeName":"J","Initials":"J"},{"@attributes":{"ValidYN":"Y"},"LastName":"Saijoh","ForeName":"Y","Initials":"Y"},{"@attributes":{"ValidYN":"Y"},"LastName":"Whitman","ForeName":"M","Initials":"M"},{"@attributes":{"ValidYN":"Y"},"LastName":"Hamada","ForeName":"H","Initials":"H"}]},"Language":["eng"],"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D016428"},"@text":"Journal Article"},{"@attributes":{"UI":"D013485"},"@text":"Research Support, Non-U.S. Gov't"}]}},"MedlineJournalInfo":{"Country":"United States","MedlineTA":"Mol Cell","NlmUniqueID":"9802571","ISSNLinking":"1097-2765"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D004268"},"@text":"DNA-Binding Proteins"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D051858"},"@text":"Forkhead Transcription Factors"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D000072576"},"@text":"Homeobox Protein Nkx-2.5"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D018398"},"@text":"Homeodomain Proteins"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D055458"},"@text":"Left-Right Determination Factors"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D055457"},"@text":"Nodal Protein"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D009687"},"@text":"Nuclear Proteins"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D051761"},"@text":"Paired Box Transcription Factors"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D014157"},"@text":"Transcription Factors"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D016212"},"@text":"Transforming Growth Factor beta"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D029867"},"@text":"Xenopus Proteins"}},{"RegistryNumber":"184787-43-7","NameOfSubstance":{"@attributes":{"UI":"D000097577"},"@text":"Homeobox Protein PITX2"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C102067"},"@text":"FOXH1 protein, Xenopus"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C510350"},"@text":"FOXH1 protein, human"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C491117"},"@text":"Foxh1 protein, mouse"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C526161"},"@text":"LEFTY1 protein, human"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C092720"},"@text":"NKX2-5 protein, Xenopus"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C095552"},"@text":"NKX2-5 protein, human"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C484469"},"@text":"Nkx2-5 protein, mouse"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C526008"},"@text":"Nodal protein, mouse"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C101485"},"@text":"homeobox protein PITX1"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C433629"},"@text":"homeobox protein PITX3"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D000818","MajorTopicYN":"N"},"@text":"Animals"}},{"DescriptorName":{"@attributes":{"UI":"D001483","MajorTopicYN":"N"},"@text":"Base Sequence"}},{"DescriptorName":{"@attributes":{"UI":"D001665","MajorTopicYN":"N"},"@text":"Binding Sites"},"QualifierName":[{"@attributes":{"UI":"Q000502","MajorTopicYN":"N"},"@text":"physiology"}]},{"DescriptorName":{"@attributes":{"UI":"D019521","MajorTopicYN":"N"},"@text":"Body Patterning"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"N"},"@text":"genetics"}]},{"DescriptorName":{"@attributes":{"UI":"D004268","MajorTopicYN":"N"},"@text":"DNA-Binding Proteins"},"QualifierName":[{"@attributes":{"UI":"Q000737","MajorTopicYN":"N"},"@text":"chemistry"},{"@attributes":{"UI":"Q000235","MajorTopicYN":"N"},"@text":"genetics"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D004742","MajorTopicYN":"N"},"@text":"Enhancer Elements, Genetic"},"QualifierName":[{"@attributes":{"UI":"Q000502","MajorTopicYN":"N"},"@text":"physiology"}]},{"DescriptorName":{"@attributes":{"UI":"D051858","MajorTopicYN":"N"},"@text":"Forkhead Transcription Factors"}},{"DescriptorName":{"@attributes":{"UI":"D018507","MajorTopicYN":"Y"},"@text":"Gene Expression Regulation, Developmental"}},{"DescriptorName":{"@attributes":{"UI":"D000072576","MajorTopicYN":"N"},"@text":"Homeobox Protein Nkx-2.5"}},{"DescriptorName":{"@attributes":{"UI":"D018398","MajorTopicYN":"N"},"@text":"Homeodomain Proteins"},"QualifierName":[{"@attributes":{"UI":"Q000737","MajorTopicYN":"N"},"@text":"chemistry"},{"@attributes":{"UI":"Q000235","MajorTopicYN":"Y"},"@text":"genetics"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D007763","MajorTopicYN":"N"},"@text":"Lac Operon"}},{"DescriptorName":{"@attributes":{"UI":"D055458","MajorTopicYN":"N"},"@text":"Left-Right Determination Factors"}},{"DescriptorName":{"@attributes":{"UI":"D051379","MajorTopicYN":"N"},"@text":"Mice"}},{"DescriptorName":{"@attributes":{"UI":"D008969","MajorTopicYN":"N"},"@text":"Molecular Sequence Data"}},{"DescriptorName":{"@attributes":{"UI":"D055457","MajorTopicYN":"N"},"@text":"Nodal Protein"}},{"DescriptorName":{"@attributes":{"UI":"D009687","MajorTopicYN":"Y"},"@text":"Nuclear Proteins"}},{"DescriptorName":{"@attributes":{"UI":"D051761","MajorTopicYN":"N"},"@text":"Paired Box Transcription Factors"}},{"DescriptorName":{"@attributes":{"UI":"D015398","MajorTopicYN":"N"},"@text":"Signal Transduction"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"N"},"@text":"genetics"}]},{"DescriptorName":{"@attributes":{"UI":"D014157","MajorTopicYN":"N"},"@text":"Transcription Factors"},"QualifierName":[{"@attributes":{"UI":"Q000737","MajorTopicYN":"N"},"@text":"chemistry"},{"@attributes":{"UI":"Q000235","MajorTopicYN":"Y"},"@text":"genetics"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D016212","MajorTopicYN":"N"},"@text":"Transforming Growth Factor beta"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"Y"},"@text":"genetics"}]},{"DescriptorName":{"@attributes":{"UI":"D019076","MajorTopicYN":"N"},"@text":"Transgenes"},"QualifierName":[{"@attributes":{"UI":"Q000502","MajorTopicYN":"N"},"@text":"physiology"}]},{"DescriptorName":{"@attributes":{"UI":"D014981","MajorTopicYN":"N"},"@text":"Xenopus"}},{"DescriptorName":{"@attributes":{"UI":"D029867","MajorTopicYN":"Y"},"@text":"Xenopus Proteins"}},{"DescriptorName":{"@attributes":{"UI":"D000097577","MajorTopicYN":"N"},"@text":"Homeobox Protein PITX2"}}]}},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"pubmed"},"Year":"2001","Month":"2","Day":"15","Hour":"11","Minute":"0"},{"@attributes":{"PubStatus":"medline"},"Year":"2001","Month":"3","Day":"27","Hour":"10","Minute":"1"},{"@attributes":{"PubStatus":"entrez"},"Year":"2001","Month":"2","Day":"15","Hour":"11","Minute":"0"}]},"PublicationStatus":"ppublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"11172719"},{"@attributes":{"IdType":"doi"},"@text":"10.1016\/s1097-2765(01)00162-9"},{"@attributes":{"IdType":"pii"},"@text":"S1097-2765(01)00162-9"}]}}}}