[{"publication_status":"published","project":[{"call_identifier":"FWF","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation","_id":"254E9036-B435-11E9-9278-68D0E5697425"}],"publisher":"IST Austria","author":[{"last_name":"Prizak","full_name":"Prizak, Roshan","first_name":"Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87"}],"file":[{"access_level":"open_access","relation":"main_file","creator":"rprizak","content_type":"application/pdf","date_created":"2019-03-06T16:05:07Z","file_name":"Thesis_final_PDFA_RoshanPrizak.pdf","open_access":1,"date_updated":"2019-03-07T07:09:23Z","file_id":"6072","file_size":20995465,"request_a_copy":0},{"request_a_copy":0,"content_type":"application/zip","date_created":"2019-03-06T16:09:39Z","file_name":"thesis_v2_merge.zip","access_level":"closed","relation":"source_file","creator":"rprizak","file_id":"6073","date_updated":"2019-08-13T13:47:25Z","file_size":85705272,"title":"Latex files","open_access":0}],"_version":52,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"189","type":"dissertation","doi":"10.15479/at:ista:th6071","date_created":"2019-03-06T16:16:10Z","creator":{"id":"4456104E-F248-11E8-B48F-1D18A9856A87","login":"rprizak"},"alternative_title":["IST Austria Thesis"],"date_published":"2019-03-11T00:00:00Z","ddc":["576"],"title":"Coevolution of transcription factors and their binding sites in sequence space","department":[{"_id":"GaTk","tree":[{"_id":"ResearchGroups"},{"_id":"IST"}]},{"tree":[{"_id":"ResearchGroups"},{"_id":"IST"}],"_id":"NiBa"}],"language":[{"iso":"eng"}],"year":"2019","abstract":[{"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. ","lang":"eng"}],"related_material":{"record":[{"status":"public","id":"1358","relation":"part_of_dissertation"},{"id":"955","status":"public","relation":"part_of_dissertation"}]},"accept":"1","status":"public","_id":"6071","citation":{"chicago":"Prizak, Roshan. <i>Coevolution of Transcription Factors and Their Binding Sites in Sequence Space</i>. IST Austria, 2019. <a href=\"https://doi.org/10.15479/at:ista:th6071\">https://doi.org/10.15479/at:ista:th6071</a>.","short":"R. Prizak, Coevolution of Transcription Factors and Their Binding Sites in Sequence Space, IST Austria, 2019.","ama":"Prizak R. <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>","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>.","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>","ieee":"R. Prizak, <i>Coevolution of transcription factors and their binding sites in sequence space</i>. IST Austria, 2019.","ista":"Prizak R. 2019. Coevolution of transcription factors and their binding sites in sequence space, IST Austria, 189p."},"month":"03","day":"11","supervisor":[{"orcid":"0000-0002-6699-1455","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","first_name":"Gašper"}],"date_updated":"2020-01-21T13:22:27Z","oa_version":"Published Version","file_date_updated":"2019-08-13T13:47:25Z"}]