MARC details
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03025ntm a22003377a 4500 |
| 003 - CONTROL NUMBER IDENTIFIER |
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| control field |
AT-ISTA |
| 005 - DATE AND TIME OF LATEST TRANSACTION |
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20190904114827.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION |
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| fixed length control field |
190819s2019 au ||||| m||| 00| 0 eng d |
| 040 ## - CATALOGING SOURCE |
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| Transcribing agency |
IST |
| 100 ## - MAIN ENTRY--PERSONAL NAME |
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| Personal name |
Prizak, Roshan |
| 9 (RLIN) |
5881 |
| 245 ## - TITLE STATEMENT |
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| Title |
Coevolution of transcription factors and their binding sites in sequence space |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. (IMPRINT) |
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| Name of publisher, distributor, etc. |
IST Austria |
| Date of publication, distribution, etc. |
2019 |
| 500 ## - GENERAL NOTE |
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| General note |
Thesis |
| 505 ## - FORMATTED CONTENTS NOTE |
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| Formatted contents note |
Abstract |
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About the Author |
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| Formatted contents note |
List of Publications |
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List of Tables |
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List of Figures |
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List of Abbreviations |
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| Formatted contents note |
0 Introduction |
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| Formatted contents note |
1 TF-DNA binding in sequence space |
| 505 ## - FORMATTED CONTENTS NOTE |
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| Formatted contents note |
2 Crosstalk in gene regulation |
| 505 ## - FORMATTED CONTENTS NOTE |
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3 General theoretical formulation of TF-BS coevolution |
| 505 ## - FORMATTED CONTENTS NOTE |
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4 Coevolution of duplicated TFs with their binding sites |
| 505 ## - FORMATTED CONTENTS NOTE |
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5 Bioinformatic analysis for the evolution of Zn-finger TFs |
| 505 ## - FORMATTED CONTENTS NOTE |
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| Formatted contents note |
Coevolution of transcription factors and their binding sites in sequence space |
| 505 ## - FORMATTED CONTENTS NOTE |
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| Formatted contents note |
Bibliography |
| 520 ## - SUMMARY, ETC. |
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| Summary, etc. |
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. |
| 856 ## - ELECTRONIC LOCATION AND ACCESS |
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| Uniform Resource Identifier |
<a href="https://doi.org/10.15479/at:ista:th6071">https://doi.org/10.15479/at:ista:th6071</a> |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) |
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| Source of classification or shelving scheme |
Dewey Decimal Classification |