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dc.contributor.advisorCharles Sagerstrӧm
dc.contributor.authorStanney, William J. III
dc.date2022-08-11T08:08:38.000
dc.date.accessioned2022-08-23T16:02:08Z
dc.date.available2022-08-23T16:02:08Z
dc.date.issued2019-08-06
dc.date.submitted2019-08-27
dc.identifier.doi10.13028/6ek2-8p41
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31266
dc.description.abstractThe TALE factors, comprising the pbx and prep/meis gene families, are transcription factors (TFs) vital to the proper formation of anterior anatomical structures during embryonic development. Although best understood as essential cofactors for tissue-specific TFs such as the hox genes during segmentation, the TALE factors also form complexes with nuclear factor Y (NFY) in the early zygote. In zebrafish, Pbx4, Prep1, and NFY are maternally deposited and can access their DNA binding sites in compact chromatin. Our results suggest that TALE/NFY complexes have a unique role in early embryonic development which is distinct from each factor’s independent functions at later stages. To characterize these TALE/NFY complexes, we employed high-throughput transcriptomic and genomic techniques in zebrafish embryos. Using dominant negatives to disrupt the function of each factor, we find that they display similar, but not identical, loss-of-function phenotypes and co-regulate genes involved in transcription regulation and embryonic development. Independently, the TALE factors regulate homeobox genes and NFY governs cilia-related genes. ChIP-seq analysis at zygotic genome activation reveals that the TALE factors occupy DECA sites adjacent to CCAAT boxes near genes expressed early in development and involved with transcription regulation. Finally, DNA elements containing TALE and NFY binding sites drive reporter gene expression in transgenic zebrafish, and disruption of TALE/NFY binding via mutation or dominant negatives eliminates this expression. Taken together, this data suggests that the TALE factors and NFY cooperate to regulate a set of development and transcription control genes in early zygotic development but also have independent roles after gastrulation.
dc.language.isoen_US
dc.rightsLicensed under a Creative Commons license
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjecttranscription
dc.subjectembryogenesis
dc.subjectmaternal
dc.subjectzygotic
dc.subjectenhancer
dc.subjectnucleosome
dc.subjectpioneer factor
dc.subjectepigenetics
dc.subjectTALE
dc.subjectNFY
dc.subjectBiochemistry
dc.subjectDevelopmental Biology
dc.subjectMolecular Biology
dc.titleThe TALE Factors and Nuclear Factor Y Cooperate to Drive Transcription at Zygotic Genome Activation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2054&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/1045
dc.legacy.embargo2020-02-29T00:00:00-08:00
dc.identifier.contextkey15214606
refterms.dateFOA2022-08-26T03:57:41Z
html.description.abstract<p>The TALE factors, comprising the <em>pbx</em> and <em>prep</em>/<em>meis</em> gene families, are transcription factors (TFs) vital to the proper formation of anterior anatomical structures during embryonic development. Although best understood as essential cofactors for tissue-specific TFs such as the <em>hox</em> genes during segmentation, the TALE factors also form complexes with nuclear factor Y (NFY) in the early zygote. In zebrafish, Pbx4, Prep1, and NFY are maternally deposited and can access their DNA binding sites in compact chromatin. Our results suggest that TALE/NFY complexes have a unique role in early embryonic development which is distinct from each factor’s independent functions at later stages.</p> <p>To characterize these TALE/NFY complexes, we employed high-throughput transcriptomic and genomic techniques in zebrafish embryos. Using dominant negatives to disrupt the function of each factor, we find that they display similar, but not identical, loss-of-function phenotypes and co-regulate genes involved in transcription regulation and embryonic development. Independently, the TALE factors regulate homeobox genes and NFY governs cilia-related genes. ChIP-seq analysis at zygotic genome activation reveals that the TALE factors occupy DECA sites adjacent to CCAAT boxes near genes expressed early in development and involved with transcription regulation. Finally, DNA elements containing TALE and NFY binding sites drive reporter gene expression in transgenic zebrafish, and disruption of TALE/NFY binding via mutation or dominant negatives eliminates this expression. Taken together, this data suggests that the TALE factors and NFY cooperate to regulate a set of development and transcription control genes in early zygotic development but also have independent roles after gastrulation.</p>
dc.identifier.submissionpathgsbs_diss/1045
dc.contributor.departmentBiochemistry and Molecular Pharmacology
dc.description.thesisprogramBiochemistry and Molecular Pharmacology
dc.identifier.orcid0000-0002-7488-7279


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