--- res: bibo_abstract: - 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. @eng bibo_authorlist: - foaf_Person: foaf_givenName: Roshan foaf_name: Prizak, Roshan foaf_surname: Prizak foaf_workInfoHomepage: http://www.librecat.org/personId=4456104E-F248-11E8-B48F-1D18A9856A87 bibo_doi: 10.15479/at:ista:th6071 dct_date: 2019^xs_gYear dct_isPartOf: - http://id.crossref.org/issn/2663-337X dct_language: eng dct_publisher: Institute of Science and Technology Austria@ dct_title: Coevolution of transcription factors and their binding sites in sequence space@ ...