{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86443"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86443","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Global Genome and Hox Cluster Conformational Programming During ESC Neuronal Development – The Role of nFGFR1 and CTCF","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Decker, Brandon; 0000-0003-3859-4337"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Stachowiak, Michal","Genetics, Genomics and Bioinformatics"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-21T17:22:29Z","date_published":"2025-02-21T17:22:29Z","updated_at":"2026-07-27T19:05:32Z","subjects":["genetics","developmental biology","bioinformatics"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/86443","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Stachowiak, Michal","Genetics, Genomics and Bioinformatics"]},{"key":"dc:creator","label":"Author","values":["Decker, Brandon; 0000-0003-3859-4337"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-21T17:22:29Z","2020"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["genetics","developmental biology","bioinformatics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/86443"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Development of mouse embryonic stem (ESC) to neuronal committed (NCC) cells involves coordinate changes in the expression of >3000 genes in a process that involves direct gene programing by the nuclear form of FGFR1 (nFGFR1). How such an immense computational task is accomplished is largely unknown. Chromatin organizers such as CTCF have been shown to be involved, but what other proteins might contribute to genome structure. FGFR1 is a protein critical for normal embryonic development through its promoter binding activities. In these studies we investigated 3D structure using the NextGen sequencing global genome Chromosome Conformation Capture HiC and HiChIP methods. Here we show that ESC and NCC have widespread differences in chromatin looping structures, FGFR1 binding, and gene expression programs on a genome-wide scale and in the exemplary Hox loci, and that nFGFR1 binding inhibition disrupts chromatin looping in the HoxA cluster. This study advances a topologically integrated genome that undergoes extensive structural remodeling as it undergoes global functional reprogramming during the development of the ESC to NCC. The remodeling of the chromatin Topologically Associated Domains (TADs) in NCC involves increased nFGFR1 binding at the TADs borders, inner and outer regions, and replacement of the CTCF-associated loops of ESC with the nFGFR1-associated loops in NCC. The changing TADs recruit genes of different ontological programs (i.e. cell proliferation supported by metabolism in ESC and transcriptional regulation of neurodevelopmental genes in NCC). We propose a \"Genome Archipelago Model\" in which TADs create transient islands of shared ontological functions that define the ontogenic process.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Global Genome and Hox Cluster Conformational Programming During ESC Neuronal Development – The Role of nFGFR1 and CTCF"]}]}],"canonical_facts":{"dc:contributor":["Stachowiak, Michal","Genetics, Genomics and Bioinformatics"],"dc:creator":["Decker, Brandon; 0000-0003-3859-4337"],"dc:date":["2025-02-21T17:22:29Z","2020"],"dc:description":["Ph.D.","Development of mouse embryonic stem (ESC) to neuronal committed (NCC) cells involves coordinate changes in the expression of >3000 genes in a process that involves direct gene programing by the nuclear form of FGFR1 (nFGFR1). How such an immense computational task is accomplished is largely unknown. Chromatin organizers such as CTCF have been shown to be involved, but what other proteins might contribute to genome structure. FGFR1 is a protein critical for normal embryonic development through its promoter binding activities. In these studies we investigated 3D structure using the NextGen sequencing global genome Chromosome Conformation Capture HiC and HiChIP methods. Here we show that ESC and NCC have widespread differences in chromatin looping structures, FGFR1 binding, and gene expression programs on a genome-wide scale and in the exemplary Hox loci, and that nFGFR1 binding inhibition disrupts chromatin looping in the HoxA cluster. This study advances a topologically integrated genome that undergoes extensive structural remodeling as it undergoes global functional reprogramming during the development of the ESC to NCC. The remodeling of the chromatin Topologically Associated Domains (TADs) in NCC involves increased nFGFR1 binding at the TADs borders, inner and outer regions, and replacement of the CTCF-associated loops of ESC with the nFGFR1-associated loops in NCC. The changing TADs recruit genes of different ontological programs (i.e. cell proliferation supported by metabolism in ESC and transcriptional regulation of neurodevelopmental genes in NCC). We propose a \"Genome Archipelago Model\" in which TADs create transient islands of shared ontological functions that define the ontogenic process.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/86443"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["genetics","developmental biology","bioinformatics"],"dc:title":["Global Genome and Hox Cluster Conformational Programming During ESC Neuronal Development – The Role of nFGFR1 and CTCF"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:32Z"}