GSBS Dissertations and Theses

ORCID ID

0000-0002-7488-7279

Publication Date

2019-08-06

Document Type

Doctoral Dissertation

Academic Program

Biochemistry and Molecular Pharmacology

Department

Biochemistry and Molecular Pharmacology

First Thesis Advisor

Charles Sagerstrӧm

Keywords

transcription, embryogenesis, maternal, zygotic, enhancer, nucleosome, pioneer factor, epigenetics, TALE, NFY

Abstract

The 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.

DOI

10.13028/6ek2-8p41

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This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Available for download on Saturday, February 29, 2020

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