{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/127333"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/127333","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Regulatory of genome maintenance","abstract":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2026-12-01","abstract_html":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2026-12-01","abstract_has_math":false,"creators":["Kurniawan, Fredy"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Cell and Developmental Biology","degree_department":null,"school":null,"contributors":["Prasanth, Supriya G","Chen, Jie","Sokac, Anna M","Raetzman, Lori T"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-10-30","date_published":"2024-10-30","updated_at":"2026-07-22T22:25:03Z","subjects":["Bend3","Transcription Repression","Polycomb Repressive Complex","H3k27me3","Differentiation","Mitosis","Nucleolus","Orc6","Phosphorylation","Replication"],"languages":["en","eng"],"rights":["Copyright 2024 Fredy Kurniawan"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/127333","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Prasanth, Supriya G","Chen, Jie","Sokac, Anna M","Raetzman, Lori T"]},{"key":"dc:creator","label":"Author","values":["Kurniawan, Fredy"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2024-10-30","2024-12"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Developmental Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Bend3","Transcription Repression","Polycomb Repressive Complex","H3k27me3","Differentiation","Mitosis","Nucleolus","Orc6","Phosphorylation","Replication"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2024 Fredy Kurniawan"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/127333"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2026-12-01","The student, Fredy Kurniawan, accepted the attached license on 2024-10-18 at 17:42.","The student, Fredy Kurniawan, submitted this Dissertation for approval on 2024-10-18 at 17:52.","This Dissertation was approved for publication on 2024-10-30 at 15:29.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21260 on 2025-03-28 at 14:42:52","Transcription regulation is an important mechanism that controls pluripotency and differentiation. Transcription factors dictate cell fate decisions by functioning cooperatively with chromatin regulators. BEND3 is a quadruple BEN domain–containing protein that associates with heterochromatin and functions as a transcriptional repressor. We find that BEND3 is highly expressed in pluripotent cells, and the induction of differentiation results in the down-regulation of BEND3. The removal of BEND3 from pluripotent cells results in cells exhibiting upregulation of the differentiation-inducing gene expression signature. We find that BEND3 binds to the promoters of differentiation-associated factors and key cell cycle regulators, including CDKN1A, encoding the cell cycle inhibitor p21, and represses the expression of differentiation-associated genes by enhancing H3K27me3 decoration at these promoters. Our results support a model in which transcription repression mediated by BEND3 is essential for normal development and to prevent differentiation. In addition, we also highlight the collaboration of BEND3 with the polycomb repressive complex in coordinating transcription repression and propose a model highlighting the relevance of the BEND3-PRC2 axis in gene regulation and chromatin organization. The human Origin Recognition Complex (ORC) is required not only for the initiation of DNA replication, but is also implicated in diverse cellular functions, including chromatin organization, centrosome biology, and cytokinesis. The smallest subunit of ORC, Orc6, is poorly conserved amongst eukaryotes. Recent studies from our laboratory have suggested that human Orc6 is not required for replication licensing, but is needed for S-phase progression. Further, ATR-dependent phosphorylation of Orc6 at T229 is implicated in DNA damage response during S-phase. In this study, we demonstrate that the CDK-dependent phosphorylation of Orc6 at T195 occurs during mitosis. While the phosphorylation at T195 does not seem to be required to exit mitosis, cells expressing the phosphomimetic T195E mutant of Orc6 impede S-phase progression. Moreover, the phosphorylated form of Orc6 associates with ORC more robustly, and Orc6 shows enhanced association with the ORC outside of G1, supporting the view that Orc6 may prevent the role of Orc1-5 in licensing outside of G1. Finally, Orc6 and the phosphorylated Orc6 localize to the nucleolar organizing centers and regulate ribosome biogenesis. Our results suggest that phosphorylated Orc6 at T195 prevents replication."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Regulatory of genome maintenance"]}]}],"canonical_facts":{"dc:contributor":["Prasanth, Supriya G","Chen, Jie","Sokac, Anna M","Raetzman, Lori T"],"dc:creator":["Kurniawan, Fredy"],"dc:date":["2024-10-30","2024-12"],"dc:description":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2026-12-01","The student, Fredy Kurniawan, accepted the attached license on 2024-10-18 at 17:42.","The student, Fredy Kurniawan, submitted this Dissertation for approval on 2024-10-18 at 17:52.","This Dissertation was approved for publication on 2024-10-30 at 15:29.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21260 on 2025-03-28 at 14:42:52","Transcription regulation is an important mechanism that controls pluripotency and differentiation. Transcription factors dictate cell fate decisions by functioning cooperatively with chromatin regulators. BEND3 is a quadruple BEN domain–containing protein that associates with heterochromatin and functions as a transcriptional repressor. We find that BEND3 is highly expressed in pluripotent cells, and the induction of differentiation results in the down-regulation of BEND3. The removal of BEND3 from pluripotent cells results in cells exhibiting upregulation of the differentiation-inducing gene expression signature. We find that BEND3 binds to the promoters of differentiation-associated factors and key cell cycle regulators, including CDKN1A, encoding the cell cycle inhibitor p21, and represses the expression of differentiation-associated genes by enhancing H3K27me3 decoration at these promoters. Our results support a model in which transcription repression mediated by BEND3 is essential for normal development and to prevent differentiation. In addition, we also highlight the collaboration of BEND3 with the polycomb repressive complex in coordinating transcription repression and propose a model highlighting the relevance of the BEND3-PRC2 axis in gene regulation and chromatin organization. The human Origin Recognition Complex (ORC) is required not only for the initiation of DNA replication, but is also implicated in diverse cellular functions, including chromatin organization, centrosome biology, and cytokinesis. The smallest subunit of ORC, Orc6, is poorly conserved amongst eukaryotes. Recent studies from our laboratory have suggested that human Orc6 is not required for replication licensing, but is needed for S-phase progression. Further, ATR-dependent phosphorylation of Orc6 at T229 is implicated in DNA damage response during S-phase. In this study, we demonstrate that the CDK-dependent phosphorylation of Orc6 at T195 occurs during mitosis. While the phosphorylation at T195 does not seem to be required to exit mitosis, cells expressing the phosphomimetic T195E mutant of Orc6 impede S-phase progression. Moreover, the phosphorylated form of Orc6 associates with ORC more robustly, and Orc6 shows enhanced association with the ORC outside of G1, supporting the view that Orc6 may prevent the role of Orc1-5 in licensing outside of G1. Finally, Orc6 and the phosphorylated Orc6 localize to the nucleolar organizing centers and regulate ribosome biogenesis. Our results suggest that phosphorylated Orc6 at T195 prevents replication."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/127333"],"dc:language":["en","eng"],"dc:rights":["Copyright 2024 Fredy Kurniawan"],"dc:subject":["Bend3","Transcription Repression","Polycomb Repressive Complex","H3k27me3","Differentiation","Mitosis","Nucleolus","Orc6","Phosphorylation","Replication"],"dc:title":["Regulatory of genome maintenance"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Cell and Developmental Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:03Z"}