Coevolution of transcription factors and their binding sites in sequence space

By: Prizak, Roshan
Material type: TextTextPublisher: IST Austria 2019Online resources: Click here to access online
Contents:
Abstract
About the Author
List of Publications
List of Tables
List of Figures
List of Abbreviations
0 Introduction
1 TF-DNA binding in sequence space
2 Crosstalk in gene regulation
3 General theoretical formulation of TF-BS coevolution
4 Coevolution of duplicated TFs with their binding sites
5 Bioinformatic analysis for the evolution of Zn-finger TFs
Coevolution of transcription factors and their binding sites in sequence space
Bibliography
Summary: Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past.
List(s) this item appears in: IST Austria Thesis
Tags from this library: No tags from this library for this title. Log in to add tags.
    Average rating: 0.0 (0 votes)
Item type Current location Call number Status Date due Barcode Item holds
Book Book Library
Available AT-ISTA#001870
Total holds: 0

Thesis

Abstract

About the Author

List of Publications

List of Tables

List of Figures

List of Abbreviations

0 Introduction

1 TF-DNA binding in sequence space

2 Crosstalk in gene regulation

3 General theoretical formulation of TF-BS coevolution

4 Coevolution of duplicated TFs with their binding sites

5 Bioinformatic analysis for the evolution of Zn-finger TFs

Coevolution of transcription factors and their binding sites in sequence space

Bibliography

Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past.

There are no comments for this item.

to post a comment.

Powered by Koha