{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10069"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10069","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Studies of the Molecular Features of Brd4-Nut and P300 That Contribute to Condensate Formation and Transcriptional Regulation","abstract":"Aberrant formation of biomolecular condensates has been proposed to play a role in several cancers. The oncogenic fusion protein Brd4-Nut drives aberrant gene expression and forms condensates in Nut Carcinoma (NC). It has not been clear how these condensates form and whether they modulate gene expression. Here, I dissected the molecular features of Brd4-Nut and a histone acetyltransferase (HAT), p300, and analyzed their contribution to condensate formation and transcriptional changes. I determined that a minimal fragment of Nut (MIN) in fusion with Brd4 is necessary and sufficient for binding to p300, and for condensate formation. A Brd4-p300 fusion protein also forms condensates and drives a transcriptional profile similar to Brd4-Nut(MIN). The intrinsically disordered regions, transcription factor - binding domains, and HAT activity of p300 all collectively contribute to condensate formation. Conversely, only HAT activity appears to be necessary to mimic the transcriptional profile of cells expressing Brd4-Nut. My results suggest that interaction of Brd4-Nut with p300 is important for aberrant condensate formation, and that multiple, yet distinct, regions of p300 contribute to condensate formation and transcriptional regulation.","abstract_html":"Aberrant formation of biomolecular condensates has been proposed to play a role in several cancers. The oncogenic fusion protein Brd4-Nut drives aberrant gene expression and forms condensates in Nut Carcinoma (NC). It has not been clear how these condensates form and whether they modulate gene expression. Here, I dissected the molecular features of Brd4-Nut and a histone acetyltransferase (HAT), p300, and analyzed their contribution to condensate formation and transcriptional changes. I determined that a minimal fragment of Nut (MIN) in fusion with Brd4 is necessary and sufficient for binding to p300, and for condensate formation. A Brd4-p300 fusion protein also forms condensates and drives a transcriptional profile similar to Brd4-Nut(MIN). The intrinsically disordered regions, transcription factor - binding domains, and HAT activity of p300 all collectively contribute to condensate formation. Conversely, only HAT activity appears to be necessary to mimic the transcriptional profile of cells expressing Brd4-Nut. My results suggest that interaction of Brd4-Nut with p300 is important for aberrant condensate formation, and that multiple, yet distinct, regions of p300 contribute to condensate formation and transcriptional regulation.","abstract_has_math":false,"creators":["Kosno, Martyna Olga"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Kohler, Jennifer J.","Tu, Benjamin","Henne, W. Mike","Brekken, Rolf A.","Liszczak, Glen","Rosen, Michael K."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-06-07T18:16:38Z","date_published":"2023-06-07T18:16:38Z","updated_at":"2026-07-24T05:52:17Z","subjects":["Carcinoma, Squamous Cell","Cell Cycle Proteins","E1A-Associated p300 Protein","Gene Expression Regulation, Neoplastic","Transcription Factors"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1381370396"],"render_values":[{"text":"1381370396","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10069","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kohler, Jennifer J.","Tu, Benjamin","Henne, W. Mike","Brekken, Rolf A.","Liszczak, Glen","Rosen, Michael K."]},{"key":"dc:creator","label":"Author","values":["Kosno, Martyna Olga"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2023-06-07T18:16:38Z","2023-05","2023-05-01T05:00:00.000Z","May 2023","2023-06-07T18:16:39Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Carcinoma, Squamous Cell","Cell Cycle Proteins","E1A-Associated p300 Protein","Gene Expression Regulation, Neoplastic","Transcription Factors"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10069","1381370396"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Aberrant formation of biomolecular condensates has been proposed to play a role in several cancers. The oncogenic fusion protein Brd4-Nut drives aberrant gene expression and forms condensates in Nut Carcinoma (NC). It has not been clear how these condensates form and whether they modulate gene expression. Here, I dissected the molecular features of Brd4-Nut and a histone acetyltransferase (HAT), p300, and analyzed their contribution to condensate formation and transcriptional changes. I determined that a minimal fragment of Nut (MIN) in fusion with Brd4 is necessary and sufficient for binding to p300, and for condensate formation. A Brd4-p300 fusion protein also forms condensates and drives a transcriptional profile similar to Brd4-Nut(MIN). The intrinsically disordered regions, transcription factor - binding domains, and HAT activity of p300 all collectively contribute to condensate formation. Conversely, only HAT activity appears to be necessary to mimic the transcriptional profile of cells expressing Brd4-Nut. My results suggest that interaction of Brd4-Nut with p300 is important for aberrant condensate formation, and that multiple, yet distinct, regions of p300 contribute to condensate formation and transcriptional regulation."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Studies of the Molecular Features of Brd4-Nut and P300 That Contribute to Condensate Formation and Transcriptional Regulation"]}]}],"canonical_facts":{"dc:contributor":["Kohler, Jennifer J.","Tu, Benjamin","Henne, W. Mike","Brekken, Rolf A.","Liszczak, Glen","Rosen, Michael K."],"dc:creator":["Kosno, Martyna Olga"],"dc:date":["2023-06-07T18:16:38Z","2023-05","2023-05-01T05:00:00.000Z","May 2023","2023-06-07T18:16:39Z"],"dc:description":["Aberrant formation of biomolecular condensates has been proposed to play a role in several cancers. The oncogenic fusion protein Brd4-Nut drives aberrant gene expression and forms condensates in Nut Carcinoma (NC). It has not been clear how these condensates form and whether they modulate gene expression. Here, I dissected the molecular features of Brd4-Nut and a histone acetyltransferase (HAT), p300, and analyzed their contribution to condensate formation and transcriptional changes. I determined that a minimal fragment of Nut (MIN) in fusion with Brd4 is necessary and sufficient for binding to p300, and for condensate formation. A Brd4-p300 fusion protein also forms condensates and drives a transcriptional profile similar to Brd4-Nut(MIN). The intrinsically disordered regions, transcription factor - binding domains, and HAT activity of p300 all collectively contribute to condensate formation. Conversely, only HAT activity appears to be necessary to mimic the transcriptional profile of cells expressing Brd4-Nut. My results suggest that interaction of Brd4-Nut with p300 is important for aberrant condensate formation, and that multiple, yet distinct, regions of p300 contribute to condensate formation and transcriptional regulation."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10069","1381370396"],"dc:language":["en"],"dc:subject":["Carcinoma, Squamous Cell","Cell Cycle Proteins","E1A-Associated p300 Protein","Gene Expression Regulation, Neoplastic","Transcription Factors"],"dc:title":["Studies of the Molecular Features of Brd4-Nut and P300 That Contribute to Condensate Formation and Transcriptional Regulation"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:17Z"}