{"id":{"repo_id":"milano","oai_identifier":"oai:air.unimi.it:2434/1159559"},"canonical_url":"https://search.dev.ndltd.org/etd/milano/oai:air.unimi.it:2434/1159559","repository":{"repo_id":"milano","name":"Università degli Studi di Milano","base_url":"https://air.unimi.it/oai/request"},"display":{"title":"THE ALTERNATIVE SPLICING OF NF-YA REGULATES MOUSE EMBRYONIC STEM CELLS DIFFERENTIATION","abstract":"Embryogenesis is governed by a fine balance between pluripotency and differentiation controlled by a handful of Transcription Factors (TFs). Some are implied in the maintenance of self-renewal and pluripotency of Embryonic Stem Cells (ESC), others drive cell lineage decisions which give rise to the entire organism. An example of these factors is NF-Y, a heterotrimeric pioneer TF promoting chromatin accessibility to other TFs to regulate gene expression. The regulatory subunit of NF-Y, NF-YA, recognizes and binds the CCAAT box motif, one of the most enriched DNA elements in enhancers and promoters of genes specifically active in ESCs. NF-YA exists in two different isoforms generated by Alternative Splicing of Exon 3. The short (NF-YAs) and the long (NF-YAl) isoforms differ from a stretch of 28-29 amino acids in the N-terminal Q-rich activation domain. Although they display identical DNA-binding properties in vitro, the two isoforms have distinct roles in several biological processes. Regarding embryogenesis, NF-YAs is the predominant isoform in undifferentiated mouse ESCs, being crucial for the regulation of pluripotency and stemness maintenance. By contrast, during Embryoid Bodies (EB) formation process, NF-YAl prevails, suggesting an implication of this specific isoform in the differentiation of mESCs. Our data strengthen the stem-related function of NF-YAs and propose a novel role of NF-YAl in mesoderm formation to shed light on the distinct functions of NF-YA isoforms in the equilibrium between pluripotency and differentiation.","abstract_html":"Embryogenesis is governed by a fine balance between pluripotency and differentiation controlled by a handful of Transcription Factors (TFs). Some are implied in the maintenance of self-renewal and pluripotency of Embryonic Stem Cells (ESC), others drive cell lineage decisions which give rise to the entire organism. An example of these factors is NF-Y, a heterotrimeric pioneer TF promoting chromatin accessibility to other TFs to regulate gene expression. The regulatory subunit of NF-Y, NF-YA, recognizes and binds the CCAAT box motif, one of the most enriched DNA elements in enhancers and promoters of genes specifically active in ESCs. NF-YA exists in two different isoforms generated by Alternative Splicing of Exon 3. The short (NF-YAs) and the long (NF-YAl) isoforms differ from a stretch of 28-29 amino acids in the N-terminal Q-rich activation domain. Although they display identical DNA-binding properties in vitro, the two isoforms have distinct roles in several biological processes. Regarding embryogenesis, NF-YAs is the predominant isoform in undifferentiated mouse ESCs, being crucial for the regulation of pluripotency and stemness maintenance. By contrast, during Embryoid Bodies (EB) formation process, NF-YAl prevails, suggesting an implication of this specific isoform in the differentiation of mESCs. Our data strengthen the stem-related function of NF-YAs and propose a novel role of NF-YAl in mesoderm formation to shed light on the distinct functions of NF-YA isoforms in the equilibrium between pluripotency and differentiation.","abstract_has_math":false,"creators":["POLETTINI, SOFIA"],"institution":"Università degli Studi di Milano","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["tutor: D. Dolfini","S. Polettini","DOLFINI, DILETTA"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-04-17","date_published":"2025-04-17","updated_at":"2026-07-27T20:19:08Z","subjects":["NF-Y, differentiation, embryoid bodies, mESCs, transcription factors, pluripotency, primitive streak, mesoderm.","Settore BIOS-14/A - Genetica"],"languages":["eng"],"rights":["info:eu-repo/semantics/embargoedAccess"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2434/1159559","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["tutor: D. Dolfini","S. 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Some are implied in the maintenance of self-renewal and pluripotency of Embryonic Stem Cells (ESC), others drive cell lineage decisions which give rise to the entire organism. An example of these factors is NF-Y, a heterotrimeric pioneer TF promoting chromatin accessibility to other TFs to regulate gene expression. The regulatory subunit of NF-Y, NF-YA, recognizes and binds the CCAAT box motif, one of the most enriched DNA elements in enhancers and promoters of genes specifically active in ESCs. NF-YA exists in two different isoforms generated by Alternative Splicing of Exon 3. The short (NF-YAs) and the long (NF-YAl) isoforms differ from a stretch of 28-29 amino acids in the N-terminal Q-rich activation domain. Although they display identical DNA-binding properties in vitro, the two isoforms have distinct roles in several biological processes. Regarding embryogenesis, NF-YAs is the predominant isoform in undifferentiated mouse ESCs, being crucial for the regulation of pluripotency and stemness maintenance. By contrast, during Embryoid Bodies (EB) formation process, NF-YAl prevails, suggesting an implication of this specific isoform in the differentiation of mESCs. Our data strengthen the stem-related function of NF-YAs and propose a novel role of NF-YAl in mesoderm formation to shed light on the distinct functions of NF-YA isoforms in the equilibrium between pluripotency and differentiation."]},{"key":"dc:title","label":"Title","values":["THE ALTERNATIVE SPLICING OF NF-YA REGULATES MOUSE EMBRYONIC STEM CELLS DIFFERENTIATION"]}]}],"canonical_facts":{"dc:contributor":["tutor: D. Dolfini","S. Polettini","DOLFINI, DILETTA"],"dc:creator":["POLETTINI, SOFIA"],"dc:date":["2025-04-17"],"dc:description":["Embryogenesis is governed by a fine balance between pluripotency and differentiation controlled by a handful of Transcription Factors (TFs). Some are implied in the maintenance of self-renewal and pluripotency of Embryonic Stem Cells (ESC), others drive cell lineage decisions which give rise to the entire organism. An example of these factors is NF-Y, a heterotrimeric pioneer TF promoting chromatin accessibility to other TFs to regulate gene expression. The regulatory subunit of NF-Y, NF-YA, recognizes and binds the CCAAT box motif, one of the most enriched DNA elements in enhancers and promoters of genes specifically active in ESCs. NF-YA exists in two different isoforms generated by Alternative Splicing of Exon 3. The short (NF-YAs) and the long (NF-YAl) isoforms differ from a stretch of 28-29 amino acids in the N-terminal Q-rich activation domain. Although they display identical DNA-binding properties in vitro, the two isoforms have distinct roles in several biological processes. Regarding embryogenesis, NF-YAs is the predominant isoform in undifferentiated mouse ESCs, being crucial for the regulation of pluripotency and stemness maintenance. By contrast, during Embryoid Bodies (EB) formation process, NF-YAl prevails, suggesting an implication of this specific isoform in the differentiation of mESCs. Our data strengthen the stem-related function of NF-YAs and propose a novel role of NF-YAl in mesoderm formation to shed light on the distinct functions of NF-YA isoforms in the equilibrium between pluripotency and differentiation."],"dc:identifier":["https://hdl.handle.net/2434/1159559"],"dc:language":["eng"],"dc:publisher":["Università degli Studi di Milano"],"dc:relation":["numberofpages:169"],"dc:rights":["info:eu-repo/semantics/embargoedAccess"],"dc:subject":["NF-Y, differentiation, embryoid bodies, mESCs, transcription factors, pluripotency, primitive streak, mesoderm.","Settore BIOS-14/A - Genetica"],"dc:title":["THE ALTERNATIVE SPLICING OF NF-YA REGULATES MOUSE EMBRYONIC STEM CELLS DIFFERENTIATION"],"dc:type":["info:eu-repo/semantics/doctoralThesis"]},"updated_at":"2026-07-27T20:19:08Z"}