Date of Completion

2-1-2019

Embargo Period

2-1-2020

Keywords

Genomics, Regulated Transcription, Chromatin, Gene Regulation, Neuron

Major Advisor

Yijun Ruan

Associate Advisor

Stormy Chamberlain

Associate Advisor

Blanka Rogina

Associate Advisor

Zhengqing Ouyang

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Remarkably, cell types sharing the same linear genome sequence express different genes and have distinct functions. 3D genomic arrangement has been demonstrated to play a critical role in this process. Fine scale organization of genes and regulatory elements within active and inactive domains underlie gene expression and disruption of this process has been shown to influence development and disease. Yet, the precise dynamics of cell type specific 3D genomic interactions mediating mammalian gene expression, such as those between enhancers and promoters, remain lacking on a genome wide level.

Neurons represent a specialized cell type known to respond to a myriad of physiological stimuli by changes in transcription of activity dependent (AD) genes. Neuron specific enhancer activation has been identified genome wide in mouse neurons during AD gene transcription, yet we lack genome wide 3D connectivity information allowing assignment of AD enhancer gene targets. Many questions about chromatin structure and how 3D structural changes influence cell type specificity and function through changes in gene expression remain unanswered due to technological limitations and the nature of biological samples required. This thesis specifically addresses such limitations focusing on application to mammalian genomes.

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