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| {{STRUCTURE_2vi6| PDB=2vi6 | SCENE= }} | | {{STRUCTURE_2vi6| PDB=2vi6 | SCENE= }} |
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| '''CRYSTAL STRUCTURE OF THE NANOG HOMEODOMAIN'''
| | ===CRYSTAL STRUCTURE OF THE NANOG HOMEODOMAIN=== |
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| ==Overview==
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| The 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_18177668}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18177668 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18177668}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Transcription factor]] | | [[Category: Transcription factor]] |
| [[Category: Transcription regulation]] | | [[Category: Transcription regulation]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 18:51:05 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 10:59:07 2008'' |