Genome-wide Analysis of Chromatin Structure across Diverse Human Cell Types

Abstract

Chromatin structure plays an important role in gene regulation, especially in differentiating the diverse cell types in humans. In this dissertation, we analyze the nucleosome positioning and open chromatin profiles genome-wide and investigate the relationship with transcription initiation, the activity of regulatory elements, and expression levels. We mainly focus on the results of DNase-seq experiments, but also employ annotations from MNase-seq, FAIRE-seq, ChIP-seq, CAGE, and RNA microarrays. Our methods are based on computational approaches including managing large data sets, statistical analysis, and machine learning. We find that different transcription initiation patterns lead to distinct chromatin structures, suggesting diverse regulatory strategies. Moreover, we present a tool for comparing genome-wide annotation tracks and evaluate DNase-seq against a unique assay for detecting open chromatin. We also demonstrate how DNase-seq can be used to successfully predict rotationally stable nucleosomes that are conserved across cell types. We conclude that DNase-seq can be used to study genome-wide chromatin structure in an effort to better understand how it regulates gene expression.