{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/5296"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/5296","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Modulation of Transcription Factor Chromatin Association and Gene Transcription Program in Embryonic Stem Cell and Triple Negative Breast Cancer by Poly (ADP-Ribose) Polymerase 1","abstract":"Pages ix-xvi are incorrectly numbered as pages xiv-xxi.","abstract_html":"Pages ix-xvi are incorrectly numbered as pages xiv-xxi.","abstract_has_math":false,"creators":["Liu, Ziying"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Zhang, Chun-Li","Kraus, W. Lee","Kim, Tae-Kyung","Morrison, Sean J.","Li, Bing"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-06-04T18:50:31Z","date_published":"2018-06-04T18:50:31Z","updated_at":"2026-07-24T05:52:08Z","subjects":["Embryonic Stem Cells","Gene Expression Regulation, Developmental","Nucleosomes","Pluripotent Stem Cells","Poly (ADP-Ribose) Polymerase-1","SOXB1 Transcription Factors"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1038532925"],"render_values":[{"text":"1038532925","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/5296","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Zhang, Chun-Li","Kraus, W. Lee","Kim, Tae-Kyung","Morrison, Sean J.","Li, Bing"]},{"key":"dc:creator","label":"Author","values":["Liu, Ziying"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-06-04T18:50:31Z","2016-05","2016-03-30","May 2016","2018-06-04T18:42:11Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Embryonic Stem Cells","Gene Expression Regulation, Developmental","Nucleosomes","Pluripotent Stem Cells","Poly (ADP-Ribose) Polymerase-1","SOXB1 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/2152.5/5296","1038532925"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Pages ix-xvi are incorrectly numbered as pages xiv-xxi.","Poly(ADP-ribose) polymerase-1 (PARP-1), also referred to as ADP-ribosyltransferase Diphtheria toxin-like 1 (ARTD1), is an abundant nuclear protein that plays key roles in a variety of nuclear processes, including the regulation of transcription. PARP-1 possesses an intrinsic enzymatic activity that catalyzes the transfer of ADP-ribose (ADPR) units from nicotinamide adenine dinucleotide (NAD+) onto target gene regulatory proteins, thereby modulating their activities. Although great strides have been made in the past decade in deciphering the seemingly opposing and varied roles of PARP-1 in gene regulation, many puzzles remain in this field. Using a combination of cell biology, molecular biology, genomics and biochemistry methods, I investigated the functions of PARP-1 in regulating gene transcription program in mouse embryonic stem cells and human triple negative breast cancer cells. I found that in mouse embryonic stem cells, PARP-1 functions as a pre-pioneering factor, stabilizing transcription factor Sox2 interaction with nucleosomes. This function is required for maintaining gene transcription program in embryonic stem cells. Depletion of PARP-1 causes disrupted embryonic stem cell gene expression profile, including decreased expression of Nanog, as well as increased expression of differentiation genes. Furthermore, using human triple negative breast cancer cells, I showed that this gene transcriptional regulation mechanism through PARP-1-Sox2 interplay is conserved in different physiological models. Interestingly, inhibiting PARylation activity causes gain of Sox2 binding to a set of genomic locations in TNBC cells, indicating that PARylation activity plays an antagonizing role in PARP-1-regulated Sox2 chromatin interaction. In summary, our results illustrate how PARP-1 can act at the level of the nucleosome to produce global effects on transcription factor binding and biologically important gene expression outcomes."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Modulation of Transcription Factor Chromatin Association and Gene Transcription Program in Embryonic Stem Cell and Triple Negative Breast Cancer by Poly (ADP-Ribose) Polymerase 1"]}]}],"canonical_facts":{"dc:contributor":["Zhang, Chun-Li","Kraus, W. Lee","Kim, Tae-Kyung","Morrison, Sean J.","Li, Bing"],"dc:creator":["Liu, Ziying"],"dc:date":["2018-06-04T18:50:31Z","2016-05","2016-03-30","May 2016","2018-06-04T18:42:11Z"],"dc:description":["Pages ix-xvi are incorrectly numbered as pages xiv-xxi.","Poly(ADP-ribose) polymerase-1 (PARP-1), also referred to as ADP-ribosyltransferase Diphtheria toxin-like 1 (ARTD1), is an abundant nuclear protein that plays key roles in a variety of nuclear processes, including the regulation of transcription. PARP-1 possesses an intrinsic enzymatic activity that catalyzes the transfer of ADP-ribose (ADPR) units from nicotinamide adenine dinucleotide (NAD+) onto target gene regulatory proteins, thereby modulating their activities. Although great strides have been made in the past decade in deciphering the seemingly opposing and varied roles of PARP-1 in gene regulation, many puzzles remain in this field. Using a combination of cell biology, molecular biology, genomics and biochemistry methods, I investigated the functions of PARP-1 in regulating gene transcription program in mouse embryonic stem cells and human triple negative breast cancer cells. I found that in mouse embryonic stem cells, PARP-1 functions as a pre-pioneering factor, stabilizing transcription factor Sox2 interaction with nucleosomes. This function is required for maintaining gene transcription program in embryonic stem cells. Depletion of PARP-1 causes disrupted embryonic stem cell gene expression profile, including decreased expression of Nanog, as well as increased expression of differentiation genes. Furthermore, using human triple negative breast cancer cells, I showed that this gene transcriptional regulation mechanism through PARP-1-Sox2 interplay is conserved in different physiological models. Interestingly, inhibiting PARylation activity causes gain of Sox2 binding to a set of genomic locations in TNBC cells, indicating that PARylation activity plays an antagonizing role in PARP-1-regulated Sox2 chromatin interaction. In summary, our results illustrate how PARP-1 can act at the level of the nucleosome to produce global effects on transcription factor binding and biologically important gene expression outcomes."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/5296","1038532925"],"dc:language":["en"],"dc:subject":["Embryonic Stem Cells","Gene Expression Regulation, Developmental","Nucleosomes","Pluripotent Stem Cells","Poly (ADP-Ribose) Polymerase-1","SOXB1 Transcription Factors"],"dc:title":["Modulation of Transcription Factor Chromatin Association and Gene Transcription Program in Embryonic Stem Cell and Triple Negative Breast Cancer by Poly (ADP-Ribose) Polymerase 1"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:08Z"}