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Eric S. Lander. Grossman, Sharon R.(Sharon Rachel) Massachusetts Institute of Technology. Department of Biology. Massachusetts Institute of Technology. Department of Biology 2020-11-06T21:08:21Z 2020-11-06T21:08:21Z 2019 2019 https://hdl.handle.net/1721.1/128406 1202775217 Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2019 Cataloged from PDF of thesis. "The Table of Contents does not accurately represent the page numbering"--Disclaimer page. Includes bibliographical references. Combinatorial gene regulation is encoded in enhancers and promoters in the form of binding sites for transcription factors (TFs), which collaboratively recruit the transcriptional machinery and drive gene expression. Using high-throughput and quantitative technologies developed by our lab and others, we studied TF binding sites in enhancers from numerous different cell types and regulatory systems, shedding light general principles of motif composition and organization in typical cellular regulatory elements. We find extensive synergy between TF binding sites, some with organizational constraints and some with flexible positioning. We demonstrate that different TFs bind at distinct positions within regulatory elements, suggesting a new type of architectural constraint in enhancers. Importantly, our analysis of both TF organization and cooperativity revealed distinctive patterns that separates TFs into potential functional classes. Together, our results suggest a structure of the regulatory code at the level of TF function and generate new hypotheses about regiospecific binding patterns and functions of TF classes within enhancers. by Sharon R. Grossman. Ph.D. Ph.D. Massachusetts Institute of Technology, Department of Biology 295 pages eng Massachusetts Institute of Technology MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided. http://dspace.mit.edu/handle/1721.1/7582 Biology. Combinatorial gene regulation by transcription factors Thesis application/pdf 2020-11-06T21:08:19Z Publication Doctoral Bio unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="02cb0029-3a96-41b5-bc6f-cee7fb764a3d"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Combinatorial gene regulation by transcription factors</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2019</PublicationDate> <Authors> <Author> <DisplayName>Grossman, Sharon R.(Sharon Rachel)</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Biology.</Keyword> <Abstract>Combinatorial gene regulation is encoded in enhancers and promoters in the form of binding sites for transcription factors (TFs), which collaboratively recruit the transcriptional machinery and drive gene expression. Using high-throughput and quantitative technologies developed by our lab and others, we studied TF binding sites in enhancers from numerous different cell types and regulatory systems, shedding light general principles of motif composition and organization in typical cellular regulatory elements. We find extensive synergy between TF binding sites, some with organizational constraints and some with flexible positioning. We demonstrate that different TFs bind at distinct positions within regulatory elements, suggesting a new type of architectural constraint in enhancers. Importantly, our analysis of both TF organization and cooperativity revealed distinctive patterns that separates TFs into potential functional classes. Together, our results suggest a structure of the regulatory code at the level of TF function and generate new hypotheses about regiospecific binding patterns and functions of TF classes within enhancers.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>