{"day":"11","page":"189","project":[{"name":"Biophysics of information processing in gene regulation","_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","call_identifier":"FWF"}],"date_created":"2019-03-06T16:16:10Z","language":[{"iso":"eng"}],"degree_awarded":"PhD","file_date_updated":"2020-07-14T12:47:18Z","publication_identifier":{"issn":["2663-337X"]},"article_processing_charge":"No","title":"Coevolution of transcription factors and their binding sites in sequence space","department":[{"_id":"GaTk"},{"_id":"NiBa"}],"date_published":"2019-03-11T00:00:00Z","oa_version":"Published Version","oa":1,"abstract":[{"lang":"eng","text":"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. "}],"type":"dissertation","supervisor":[{"first_name":"Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper"}],"publisher":"Institute of Science and Technology Austria","file":[{"content_type":"application/pdf","file_name":"Thesis_final_PDFA_RoshanPrizak.pdf","relation":"main_file","checksum":"e60a72de35d270b31f1a23d50f224ec0","creator":"rprizak","date_created":"2019-03-06T16:05:07Z","file_size":20995465,"date_updated":"2020-07-14T12:47:18Z","access_level":"open_access","file_id":"6072"},{"content_type":"application/zip","relation":"source_file","file_name":"thesis_v2_merge.zip","title":"Latex files","checksum":"67c2630333d05ebafef5f018863a8465","creator":"rprizak","file_size":85705272,"date_created":"2019-03-06T16:09:39Z","date_updated":"2020-07-14T12:47:18Z","access_level":"closed","file_id":"6073"}],"year":"2019","_id":"6071","alternative_title":["ISTA Thesis"],"doi":"10.15479/at:ista:th6071","date_updated":"2023-09-22T10:00:48Z","has_accepted_license":"1","author":[{"full_name":"Prizak, Roshan","first_name":"Roshan","last_name":"Prizak","id":"4456104E-F248-11E8-B48F-1D18A9856A87"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","related_material":{"record":[{"id":"1358","relation":"part_of_dissertation","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"955"}]},"status":"public","publication_status":"published","month":"03","citation":{"ieee":"R. Prizak, “Coevolution of transcription factors and their binding sites in sequence space,” Institute of Science and Technology Austria, 2019.","short":"R. Prizak, Coevolution of Transcription Factors and Their Binding Sites in Sequence Space, Institute of Science and Technology Austria, 2019.","apa":"Prizak, R. (2019). <i>Coevolution of transcription factors and their binding sites in sequence space</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:th6071\">https://doi.org/10.15479/at:ista:th6071</a>","ama":"Prizak R. Coevolution of transcription factors and their binding sites in sequence space. 2019. doi:<a href=\"https://doi.org/10.15479/at:ista:th6071\">10.15479/at:ista:th6071</a>","chicago":"Prizak, Roshan. “Coevolution of Transcription Factors and Their Binding Sites in Sequence Space.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/at:ista:th6071\">https://doi.org/10.15479/at:ista:th6071</a>.","mla":"Prizak, Roshan. <i>Coevolution of Transcription Factors and Their Binding Sites in Sequence Space</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/at:ista:th6071\">10.15479/at:ista:th6071</a>.","ista":"Prizak R. 2019. Coevolution of transcription factors and their binding sites in sequence space. Institute of Science and Technology Austria."},"ddc":["576"]}