{"date_published":"2019-03-11T00:00:00Z","page":"189","language":[{"iso":"eng"}],"publication_status":"published","has_accepted_license":"1","alternative_title":["IST Austria Thesis"],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["576"],"date_updated":"2021-01-12T08:22:11Z","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. "}],"title":"Coevolution of transcription factors and their binding sites in sequence space","supervisor":[{"last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","first_name":"Gašper","orcid":"0000-0002-6699-1455"}],"_id":"6071","oa_version":"Published Version","month":"03","department":[{"_id":"GaTk"},{"_id":"NiBa"}],"type":"dissertation","date_created":"2019-03-06T16:16:10Z","file":[{"creator":"rprizak","file_name":"Thesis_final_PDFA_RoshanPrizak.pdf","date_created":"2019-03-06T16:05:07Z","checksum":"e60a72de35d270b31f1a23d50f224ec0","file_size":20995465,"file_id":"6072","relation":"main_file","access_level":"open_access","date_updated":"2020-07-14T12:47:18Z","content_type":"application/pdf"},{"creator":"rprizak","file_name":"thesis_v2_merge.zip","checksum":"67c2630333d05ebafef5f018863a8465","file_size":85705272,"date_created":"2019-03-06T16:09:39Z","relation":"source_file","file_id":"6073","title":"Latex files","date_updated":"2020-07-14T12:47:18Z","access_level":"closed","content_type":"application/zip"}],"project":[{"name":"Biophysics of information processing in gene regulation","call_identifier":"FWF","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425"}],"oa":1,"year":"2019","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"1358"},{"relation":"part_of_dissertation","status":"public","id":"955"}]},"author":[{"full_name":"Prizak, Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87","last_name":"Prizak","first_name":"Roshan"}],"publisher":"IST Austria","file_date_updated":"2020-07-14T12:47:18Z","citation":{"chicago":"Prizak, Roshan. “Coevolution of Transcription Factors and Their Binding Sites in Sequence Space.” IST Austria, 2019. <a href=\"https://doi.org/10.15479/at:ista:th6071\">https://doi.org/10.15479/at:ista:th6071</a>.","ieee":"R. Prizak, “Coevolution of transcription factors and their binding sites in sequence space,” IST Austria, 2019.","mla":"Prizak, Roshan. <i>Coevolution of Transcription Factors and Their Binding Sites in Sequence Space</i>. IST Austria, 2019, doi:<a href=\"https://doi.org/10.15479/at:ista:th6071\">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>","ista":"Prizak R. 2019. Coevolution of transcription factors and their binding sites in sequence space. IST Austria.","short":"R. Prizak, Coevolution of Transcription Factors and Their Binding Sites in Sequence Space, IST Austria, 2019.","apa":"Prizak, R. (2019). <i>Coevolution of transcription factors and their binding sites in sequence space</i>. IST Austria. <a href=\"https://doi.org/10.15479/at:ista:th6071\">https://doi.org/10.15479/at:ista:th6071</a>"},"day":"11","doi":"10.15479/at:ista:th6071"}