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Date of Award

Summer 8-15-2017

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

The epigenome orchestrates many biological processes in higher eukaryotes by providing unique gene expression instruction in each cell type. However, we are still far from the complete understanding of the particular epigenetic dynamics required for proper cellular differentiation and lineage specification during development. This dissertation explores the dynamic epigenetic changes in early development and in tissue regeneration using zebrafish as a model organism. First, I identify genomic targets that exhibit programmed DNA methylation change during zebrafish early development. These developmental stage-specific differentially methylated regions (DMRs) have multiple signatures of distal developmental enhancers. Their methylation dynamic patterns correlate with their target gene expression much stronger than promoter methylation dynamics. I use transgenic zebrafish reporter assays to show the functional enhancer activities of these developmental stage-specific DMRs in live zebrafish embryos. I exploit these methylation dynamics to reconstruct putative gene regulatory networks important for organogenesis in developing zebrafish embryos. Second, I explore epigenomic dynamics of the osteoblast lineage cells in regenerating zebrafish fin. I investigate how different epigenetic marks contribute to initiating regeneration machinery along with keeping cell identity during tissue regeneration. In summary, this dissertation improves our understanding of how the epigenome regulates cell type specific transcription in development and regeneration by integrating functional epigenomics with developmental biology.

Language

English (en)

Chair and Committee

Ting Wang

Committee Members

Douglas Chalker, Barak Cohen, Stephen Johnson, Kelly Monk,

Comments

Permanent URL: https://doi.org/10.7936/K7736QBW

Available for download on Monday, August 17, 2037

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