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dc.contributor.authorDe Masi, Federico
dc.contributor.authorGrove, Christian A.
dc.contributor.authorVedenko, Anastasia
dc.contributor.authorAlibés, Andreu
dc.contributor.authorGisselbrecht, Stephen S.
dc.contributor.authorSerrano, Luis
dc.contributor.authorBulyk, Martha L.
dc.contributor.authorWalhout, Albertha J. M.
dc.date2022-08-11T08:10:15.000
dc.date.accessioned2022-08-23T17:01:09Z
dc.date.available2022-08-23T17:01:09Z
dc.date.issued2011-06-01
dc.date.submitted2011-08-01
dc.identifier.citationNucleic Acids Res. 2011 Jun 1;39(11):4553-4563. Epub 2011 Feb 18. <a href="http://dx.doi.org/10.1093/nar/gkr070">Link to article on publisher's site</a>
dc.identifier.issn0305-1048 (Linking)
dc.identifier.doi10.1093/nar/gkr070
dc.identifier.pmid21335608
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43945
dc.description.abstractNumerous efforts are underway to determine gene regulatory networks that describe physical relationships between transcription factors (TFs) and their target DNA sequences. Members of paralogous TF families typically recognize similar DNA sequences. Knowledge of the molecular determinants of protein-DNA recognition by paralogous TFs is of central importance for understanding how small differences in DNA specificities can dictate target gene selection. Previously, we determined the in vitro DNA binding specificities of 19 Caenorhabditis elegans basic helix-loop-helix (bHLH) dimers using protein binding microarrays. These TFs bind E-box (CANNTG) and E-box-like sequences. Here, we combine these data with logics, bHLH-DNA co-crystal structures and computational modeling to infer which bHLH monomer can interact with which CAN E-box half-site and we identify a critical residue in the protein that dictates this specificity. Validation experiments using mutant bHLH proteins provide support for our inferences. Our study provides insights into the mechanisms of DNA recognition by bHLH dimers as well as a blueprint for system-level studies of the DNA binding determinants of other TF families in different model organisms and humans.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=21335608&dopt=Abstract">Link to Article in PubMed</a>
dc.rights© The Author(s) 2011. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.subjectGene Regulatory Networks
dc.subjectTranscription Factors
dc.subjectBasic Helix-Loop-Helix Transcription Factors
dc.subjectDNA-Binding Proteins
dc.subjectGenetics and Genomics
dc.titleUsing a structural and logics systems approach to infer bHLH-DNA binding specificity determinants
dc.typeJournal Article
dc.source.journaltitleNucleic acids research
dc.source.volume39
dc.source.issue11
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1156&amp;context=pgfe_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pgfe_pp/156
dc.identifier.contextkey2124691
refterms.dateFOA2022-08-23T17:01:09Z
html.description.abstract<p>Numerous efforts are underway to determine gene regulatory networks that describe physical relationships between transcription factors (TFs) and their target DNA sequences. Members of paralogous TF families typically recognize similar DNA sequences. Knowledge of the molecular determinants of protein-DNA recognition by paralogous TFs is of central importance for understanding how small differences in DNA specificities can dictate target gene selection. Previously, we determined the in vitro DNA binding specificities of 19 Caenorhabditis elegans basic helix-loop-helix (bHLH) dimers using protein binding microarrays. These TFs bind E-box (CANNTG) and E-box-like sequences. Here, we combine these data with logics, bHLH-DNA co-crystal structures and computational modeling to infer which bHLH monomer can interact with which CAN E-box half-site and we identify a critical residue in the protein that dictates this specificity. Validation experiments using mutant bHLH proteins provide support for our inferences. Our study provides insights into the mechanisms of DNA recognition by bHLH dimers as well as a blueprint for system-level studies of the DNA binding determinants of other TF families in different model organisms and humans.</p>
dc.identifier.submissionpathpgfe_pp/156
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentProgram in Gene Function and Expression
dc.source.pages4553-4563


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