{"id":{"repo_id":"penn","oai_identifier":"oai:repository.upenn.edu:20.500.14332/61434"},"canonical_url":"https://search.dev.ndltd.org/etd/penn/oai:repository.upenn.edu:20.500.14332/61434","repository":{"repo_id":"penn","name":"University of Pennsylvania","base_url":"https://repository.upenn.edu/server/oai/request"},"display":{"title":"The Functional Role for Chromatin Loops in Gene Expression Control During Human Neuron Maturation","abstract":"The causal link among higher-order chromatin loops, CTCF occupancy, and mRNA levels in post-mitotic human neurons remains an open question. Here, we summarize the field of epigenetics and chromatin in neuroscience, examine neural model systems, and build an auxin-inducible degron to deplete the architectural protein CTCF and disrupt loops genome-wide on short time scales during human induced pluripotent stem cell (iPSC)-derived post-mitotic neuronal maturation. We find thousands of ablated and hundreds of ectopically formed loops upon auxin treatment in post-mitotic neurons. By contrast to previous reports in dividing cell lines, disruption of CTCF-mediated enhancer-promoter and promoter-promoter loops significantly reduces mRNA levels of critical synaptic plasticity and neural cell adhesion genes. Upon pharmacological stimulation, CTCF depleted neurons exhibit defective activity-dependent gene expression. Our data uncover CTCF-mediated loops as an epigenetic shield against dysregulation of synaptic gene expression during the maturation of human neurons.","abstract_html":"The causal link among higher-order chromatin loops, CTCF occupancy, and mRNA levels in post-mitotic human neurons remains an open question. Here, we summarize the field of epigenetics and chromatin in neuroscience, examine neural model systems, and build an auxin-inducible degron to deplete the architectural protein CTCF and disrupt loops genome-wide on short time scales during human induced pluripotent stem cell (iPSC)-derived post-mitotic neuronal maturation. We find thousands of ablated and hundreds of ectopically formed loops upon auxin treatment in post-mitotic neurons. By contrast to previous reports in dividing cell lines, disruption of CTCF-mediated enhancer-promoter and promoter-promoter loops significantly reduces mRNA levels of critical synaptic plasticity and neural cell adhesion genes. Upon pharmacological stimulation, CTCF depleted neurons exhibit defective activity-dependent gene expression. Our data uncover CTCF-mediated loops as an epigenetic shield against dysregulation of synaptic gene expression during the maturation of human neurons.","abstract_has_math":false,"creators":["Nikish, Alexandria"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Cohen, Yale"],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025","date_published":"2025","updated_at":"2026-07-24T03:47:06Z","subjects":["Engineering","Genetics and Genomics"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://repository.upenn.edu/handle/20.500.14332/61434","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Cohen, Yale"]},{"key":"dc:creator","label":"Author","values":["Nikish, Alexandria"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-06-11T19:19:48Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-06-11T19:19:48Z"]},{"key":"dc:date.issued","label":"Date","values":["2025"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation/Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Engineering","Genetics and Genomics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://repository.upenn.edu/handle/20.500.14332/61434"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The causal link among higher-order chromatin loops, CTCF occupancy, and mRNA levels in post-mitotic human neurons remains an open question. Here, we summarize the field of epigenetics and chromatin in neuroscience, examine neural model systems, and build an auxin-inducible degron to deplete the architectural protein CTCF and disrupt loops genome-wide on short time scales during human induced pluripotent stem cell (iPSC)-derived post-mitotic neuronal maturation. We find thousands of ablated and hundreds of ectopically formed loops upon auxin treatment in post-mitotic neurons. By contrast to previous reports in dividing cell lines, disruption of CTCF-mediated enhancer-promoter and promoter-promoter loops significantly reduces mRNA levels of critical synaptic plasticity and neural cell adhesion genes. Upon pharmacological stimulation, CTCF depleted neurons exhibit defective activity-dependent gene expression. Our data uncover CTCF-mediated loops as an epigenetic shield against dysregulation of synaptic gene expression during the maturation of human neurons."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy (PhD)"]},{"key":"dc:title","label":"Title","values":["The Functional Role for Chromatin Loops in Gene Expression Control During Human Neuron Maturation"]}]}],"canonical_facts":{"dc:contributor.advisor":["Cohen, Yale"],"dc:creator":["Nikish, Alexandria"],"dc:date.accessioned":["2025-06-11T19:19:48Z"],"dc:date.available":["2025-06-11T19:19:48Z"],"dc:date.issued":["2025"],"dc:description.abstract":["The causal link among higher-order chromatin loops, CTCF occupancy, and mRNA levels in post-mitotic human neurons remains an open question. Here, we summarize the field of epigenetics and chromatin in neuroscience, examine neural model systems, and build an auxin-inducible degron to deplete the architectural protein CTCF and disrupt loops genome-wide on short time scales during human induced pluripotent stem cell (iPSC)-derived post-mitotic neuronal maturation. We find thousands of ablated and hundreds of ectopically formed loops upon auxin treatment in post-mitotic neurons. By contrast to previous reports in dividing cell lines, disruption of CTCF-mediated enhancer-promoter and promoter-promoter loops significantly reduces mRNA levels of critical synaptic plasticity and neural cell adhesion genes. Upon pharmacological stimulation, CTCF depleted neurons exhibit defective activity-dependent gene expression. Our data uncover CTCF-mediated loops as an epigenetic shield against dysregulation of synaptic gene expression during the maturation of human neurons."],"dc:description.degree":["Doctor of Philosophy (PhD)"],"dc:identifier.uri":["https://repository.upenn.edu/handle/20.500.14332/61434"],"dc:language.iso":["en"],"dc:subject":["Engineering","Genetics and Genomics"],"dc:title":["The Functional Role for Chromatin Loops in Gene Expression Control During Human Neuron Maturation"],"dc:type":["Dissertation/Thesis"]},"updated_at":"2026-07-24T03:47:06Z"}