Date of Completion

10-28-2019

Embargo Period

10-28-2019

Keywords

gene expression, regulation, epigenetic, post-transcription, and translation

Major Advisor

Zhengqing Ouyang

Associate Advisor

Yuping Zhang

Associate Advisor

Ion Mandoiu

Field of Study

Biomedical Engineering

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Regulation of gene expression, through which cells increase or decrease the gene products, is an essential part of development, which not only determines the cellular differentiation but also responds to the environmental changes. A wide range of gene regulation mechanisms are involved in two major processes, from Deoxyribonucleic acid (DNA) to Ribonucleic acid (RNA), and from RNA to protein, also known as transcription and translation, respectively. Though the regulation of gene expression is not fully understood, this complex process has been characterized to several major steps, which includes epigenetic regulation, transcriptional regulation, post-transcriptional regulation and translational regulation. The present study covers three main projects related to three of the aforementioned steps of gene regulation. First, we study the DNA methylation dynamics in the bovine early embryos. To understand the epigenetic reprogramming and regulation in the embryonic development, we characterize the methylation process at the single-base level in early embryos. Second, we develop a novel method, called Protein-RNA Association Strength (PRAS), to predict the functional targets of RNA-Binding Proteins (RBPs) that play important roles in the regulation of gene expression in the post-transcriptional process. The development of various Cross-linking and immunoprecipitation with high-throughput sequencing (CLIP-seq) data makes it possible to investigate the transcriptomic binding sites of RBPs. We aim to fill the gap between the peak-calling methods and the interpretation of RBPs’ biological functions based on CLIP-seq data. Third, we study the regulation of c-MYC on the mRNA translation. The oncogenic c-MYC (MYC) transcription factor has broad effects on gene expression and cell behavior. We study how MYC affects the global translation of mRNAs and the translation start-site usage in the human lymphoma cell line. In sum, we perform data analysis and methodology development in these three specific projects related to the regulation of gene expression, which will help us better understand the central dogma of biology.

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