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Article: Crystal Structure and DNA Binding of the Homeodomain of the Stem Cell Transcription Factor Nanog

TitleCrystal Structure and DNA Binding of the Homeodomain of the Stem Cell Transcription Factor Nanog
Authors
Keywordshomeodomain
transcription factor
pluripotency
Nanog
DNA binding
Issue Date2008
Citation
Journal of Molecular Biology, 2008, v. 376, n. 3, p. 758-770 How to Cite?
AbstractThe transcription factor Nanog is an upstream regulator in early mammalian development and a key determinant of pluripotency in embryonic stem cells. Nanog binds to promoter elements of hundreds of target genes and regulates their expression by an as yet unknown mechanism. Here, we report the crystal structure of the murine Nanog homeodomain (HD) and analysis of its interaction with a DNA element derived from the Tcf3 promoter. Two Nanog amino acid pairs, unique among HD sequences, appear to affect the mechanism of nonspecific DNA recognition as well as maintain the integrity of the structural scaffold. To assess selective DNA recognition by Nanog, we performed electrophoretic mobility shift assays using a panel of modified DNA binding sites and found that Nanog HD preferentially binds the TAAT(G/T)(G/T) motif. A series of rational mutagenesis experiments probing the role of six variant residues of Nanog on its DNA binding function establish their role in affecting binding affinity but not binding specificity. Together, the structural and functional evidence establish Nanog as a distant member of a Q50-type HD despite having considerable variation at the sequence level. © 2007 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/253101
ISSN
2020 Impact Factor: 5.469
2020 SCImago Journal Rankings: 3.189
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJauch, Ralf-
dc.contributor.authorNg, Calista Keow Leng-
dc.contributor.authorSaikatendu, Kumar Singh-
dc.contributor.authorStevens, Raymond C.-
dc.contributor.authorKolatkar, Prasanna R.-
dc.date.accessioned2018-05-11T05:38:36Z-
dc.date.available2018-05-11T05:38:36Z-
dc.date.issued2008-
dc.identifier.citationJournal of Molecular Biology, 2008, v. 376, n. 3, p. 758-770-
dc.identifier.issn0022-2836-
dc.identifier.urihttp://hdl.handle.net/10722/253101-
dc.description.abstractThe transcription factor Nanog is an upstream regulator in early mammalian development and a key determinant of pluripotency in embryonic stem cells. Nanog binds to promoter elements of hundreds of target genes and regulates their expression by an as yet unknown mechanism. Here, we report the crystal structure of the murine Nanog homeodomain (HD) and analysis of its interaction with a DNA element derived from the Tcf3 promoter. Two Nanog amino acid pairs, unique among HD sequences, appear to affect the mechanism of nonspecific DNA recognition as well as maintain the integrity of the structural scaffold. To assess selective DNA recognition by Nanog, we performed electrophoretic mobility shift assays using a panel of modified DNA binding sites and found that Nanog HD preferentially binds the TAAT(G/T)(G/T) motif. A series of rational mutagenesis experiments probing the role of six variant residues of Nanog on its DNA binding function establish their role in affecting binding affinity but not binding specificity. Together, the structural and functional evidence establish Nanog as a distant member of a Q50-type HD despite having considerable variation at the sequence level. © 2007 Elsevier Ltd. All rights reserved.-
dc.languageeng-
dc.relation.ispartofJournal of Molecular Biology-
dc.subjecthomeodomain-
dc.subjecttranscription factor-
dc.subjectpluripotency-
dc.subjectNanog-
dc.subjectDNA binding-
dc.titleCrystal Structure and DNA Binding of the Homeodomain of the Stem Cell Transcription Factor Nanog-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jmb.2007.11.091-
dc.identifier.pmid18177668-
dc.identifier.scopuseid_2-s2.0-38649124339-
dc.identifier.volume376-
dc.identifier.issue3-
dc.identifier.spage758-
dc.identifier.epage770-
dc.identifier.isiWOS:000253354900014-
dc.identifier.issnl0022-2836-

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