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Title:Tracing the evolution of lineage-specific transcription factor binding sites in a birth-death framework
Author(s):Zhang, Yang
Advisor(s):Ma, Jian; Nahrstedt, Klara
Department / Program:Bioengineering
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Transcription factor binding sites (TFBS)
Cis-regulatory element
Abstract:Changes in cis-regulatory element composition that result in novel patterns of gene expression are thought to be a major contributor to the evolution of lineage-specific traits. Although transcription factor binding events show substantial variation across species, most computational approaches to study regulatory elements focus primarily upon highly conserved sites, and rely heavily upon multiple sequence alignments. However, sequence conservation based approaches have limited ability to detect lineage-specific elements that could contribute to species-specific traits. In this thesis, we describe a novel framework that utilizes a birth-death model to trace the evolution of lineage-specific binding sites without relying on detailed base-by-base cross-species alignments. Our model was applied to analyze the evolution of binding sites based on the ChIP-seq data for six transcription factors (GATA1, SOX2, CTCF, MYC, MAX, ETS1) along the lineage toward human after human-mouse common ancestor. We estimate that a substantial fraction of binding sites (∼58-79% for each factor) in humans have origins since the divergence with mouse. Over 15% of all binding sites are unique to hominids. Such elements are often enriched near genes associated with neural-related functions and pathways, and harbor more common SNPs than older binding sites in the human genome. These results support the ability of our method to identify lineage-specific regulatory elements and help understand their roles in shaping variation in gene regulation across species.
Issue Date:2016-04-28
Rights Information:Copyright 2016 Yang Zhang
Date Available in IDEALS:2016-07-07
Date Deposited:2016-05

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