{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/113207"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/113207","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Genomic and microscopic dissection of large-scale chromatin compaction","abstract":"Large-scale chromatin compaction varies across the human genome, and these variations correlate with differences in transcriptional activity in a limited number of model systems. However, without validated genome-wide methods directly measuring large-scale chromatin compaction, the degree to which this level of chromatin organization correlates with defined features of genome organization remains unknown. Existing methods assess chromatin compaction indirectly, based on, for example, the accessibility of DNA to enzymes or susceptibility to mechanical shear, and probe lower--level chromatin organization, primarily at the nucleosome level. Therefore, these existing measures of chromatin compaction may not translate to measurements of large-scale chromatin compaction. In this dissertation I explore new methods for measuring large-scale chromatin compaction using genomic and microcopic tools. I have developed a new genomic method, based on TSA-seq, to measure chromatin compaction. TSA-Seq is a genomic method that directly probes the average physical distances of chromosome loci relative to different nuclear structures. Here I use the first derivative, or slope, of the TSA-Seq signal to identify unusually decondensed large-scale chromatin domains (DLCDs). These DLCDs have an average size of ~70 kb and correlate with nearby enrichment of active chromatin marks, enhancers and especially super-enhancers, and cohesin and CTCF binding sites. They map closely to a large fraction of genome organization domain boundaries identified by Hi-C, LAD/innerLAD boundaries defined by lamin B1 DamID, and rapid transitions in the Hi-C principal eigenvector signal. Moreover, cluster analysis reveals DLCDs map most frequently to divisions between chromatin domains of varying epigenetic marks. To validate the existence of DLCDs, I have created a digital image processing package, Angler, for analyzing DNA--FISH experiments with minimal supervision using established computer vision algorithms. Angler can measure spatial properties of FISH loci in a high throughput manner. In conclusion, my results demonstrate the non-random placement of large-scale chromatin decondensed regions, which may contribute to the functional division of the genome into discrete and independently-regulated chromatin domains.","abstract_html":"Large-scale chromatin compaction varies across the human genome, and these variations correlate with differences in transcriptional activity in a limited number of model systems. However, without validated genome-wide methods directly measuring large-scale chromatin compaction, the degree to which this level of chromatin organization correlates with defined features of genome organization remains unknown. Existing methods assess chromatin compaction indirectly, based on, for example, the accessibility of DNA to enzymes or susceptibility to mechanical shear, and probe lower--level chromatin organization, primarily at the nucleosome level. Therefore, these existing measures of chromatin compaction may not translate to measurements of large-scale chromatin compaction. In this dissertation I explore new methods for measuring large-scale chromatin compaction using genomic and microcopic tools. I have developed a new genomic method, based on TSA-seq, to measure chromatin compaction. TSA-Seq is a genomic method that directly probes the average physical distances of chromosome loci relative to different nuclear structures. Here I use the first derivative, or slope, of the TSA-Seq signal to identify unusually decondensed large-scale chromatin domains (DLCDs). These DLCDs have an average size of ~70 kb and correlate with nearby enrichment of active chromatin marks, enhancers and especially super-enhancers, and cohesin and CTCF binding sites. They map closely to a large fraction of genome organization domain boundaries identified by Hi-C, LAD/innerLAD boundaries defined by lamin B1 DamID, and rapid transitions in the Hi-C principal eigenvector signal. Moreover, cluster analysis reveals DLCDs map most frequently to divisions between chromatin domains of varying epigenetic marks. To validate the existence of DLCDs, I have created a digital image processing package, Angler, for analyzing DNA--FISH experiments with minimal supervision using established computer vision algorithms. Angler can measure spatial properties of FISH loci in a high throughput manner. In conclusion, my results demonstrate the non-random placement of large-scale chromatin decondensed regions, which may contribute to the functional division of the genome into discrete and independently-regulated chromatin domains.","abstract_has_math":false,"creators":["Gholamalamdari, Omid"],"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":["Belmont, Andrew S","Brieher, William M","Freeman, Brian C","Sinha, Saurabh"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-01-12T22:35:18Z","date_published":"2022-01-12T22:35:18Z","updated_at":"2026-07-22T22:24:53Z","subjects":["chromatin structure","compaction","genome organization"],"languages":["en"],"rights":["Copyright 2021 Omid Gholamalamdari"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/113207","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Belmont, Andrew S","Brieher, William M","Freeman, Brian C","Sinha, Saurabh"]},{"key":"dc:creator","label":"Author","values":["Gholamalamdari, Omid"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-01-12T22:35:18Z","2024-01-12T22:35:30Z","2021-07-15","2021-08"]},{"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":["chromatin structure","compaction","genome organization"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2021 Omid Gholamalamdari"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/113207"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Large-scale chromatin compaction varies across the human genome, and these variations correlate with differences in transcriptional activity in a limited number of model systems. However, without validated genome-wide methods directly measuring large-scale chromatin compaction, the degree to which this level of chromatin organization correlates with defined features of genome organization remains unknown. Existing methods assess chromatin compaction indirectly, based on, for example, the accessibility of DNA to enzymes or susceptibility to mechanical shear, and probe lower--level chromatin organization, primarily at the nucleosome level. Therefore, these existing measures of chromatin compaction may not translate to measurements of large-scale chromatin compaction. In this dissertation I explore new methods for measuring large-scale chromatin compaction using genomic and microcopic tools. I have developed a new genomic method, based on TSA-seq, to measure chromatin compaction. TSA-Seq is a genomic method that directly probes the average physical distances of chromosome loci relative to different nuclear structures. Here I use the first derivative, or slope, of the TSA-Seq signal to identify unusually decondensed large-scale chromatin domains (DLCDs). These DLCDs have an average size of ~70 kb and correlate with nearby enrichment of active chromatin marks, enhancers and especially super-enhancers, and cohesin and CTCF binding sites. They map closely to a large fraction of genome organization domain boundaries identified by Hi-C, LAD/innerLAD boundaries defined by lamin B1 DamID, and rapid transitions in the Hi-C principal eigenvector signal. Moreover, cluster analysis reveals DLCDs map most frequently to divisions between chromatin domains of varying epigenetic marks. To validate the existence of DLCDs, I have created a digital image processing package, Angler, for analyzing DNA--FISH experiments with minimal supervision using established computer vision algorithms. Angler can measure spatial properties of FISH loci in a high throughput manner. In conclusion, my results demonstrate the non-random placement of large-scale chromatin decondensed regions, which may contribute to the functional division of the genome into discrete and independently-regulated chromatin domains.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-08-01","The student, Omid Gholamalamdari, accepted the attached license on 2021-07-15 at 15:43.","The student, Omid Gholamalamdari, submitted this Dissertation for approval on 2021-07-15 at 15:53.","This Dissertation was approved for publication on 2021-07-15 at 16:36.","DSpace SAF Submission Ingestion Package generated from Vireo submission #16967 on 2022-01-12 at 12:55:22","Made available in DSpace on 2022-01-12T22:35:18Z (GMT). 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However, without validated genome-wide methods directly measuring large-scale chromatin compaction, the degree to which this level of chromatin organization correlates with defined features of genome organization remains unknown. Existing methods assess chromatin compaction indirectly, based on, for example, the accessibility of DNA to enzymes or susceptibility to mechanical shear, and probe lower--level chromatin organization, primarily at the nucleosome level. Therefore, these existing measures of chromatin compaction may not translate to measurements of large-scale chromatin compaction. In this dissertation I explore new methods for measuring large-scale chromatin compaction using genomic and microcopic tools. I have developed a new genomic method, based on TSA-seq, to measure chromatin compaction. TSA-Seq is a genomic method that directly probes the average physical distances of chromosome loci relative to different nuclear structures. Here I use the first derivative, or slope, of the TSA-Seq signal to identify unusually decondensed large-scale chromatin domains (DLCDs). These DLCDs have an average size of ~70 kb and correlate with nearby enrichment of active chromatin marks, enhancers and especially super-enhancers, and cohesin and CTCF binding sites. They map closely to a large fraction of genome organization domain boundaries identified by Hi-C, LAD/innerLAD boundaries defined by lamin B1 DamID, and rapid transitions in the Hi-C principal eigenvector signal. Moreover, cluster analysis reveals DLCDs map most frequently to divisions between chromatin domains of varying epigenetic marks. To validate the existence of DLCDs, I have created a digital image processing package, Angler, for analyzing DNA--FISH experiments with minimal supervision using established computer vision algorithms. Angler can measure spatial properties of FISH loci in a high throughput manner. In conclusion, my results demonstrate the non-random placement of large-scale chromatin decondensed regions, which may contribute to the functional division of the genome into discrete and independently-regulated chromatin domains.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-08-01","The student, Omid Gholamalamdari, accepted the attached license on 2021-07-15 at 15:43.","The student, Omid Gholamalamdari, submitted this Dissertation for approval on 2021-07-15 at 15:53.","This Dissertation was approved for publication on 2021-07-15 at 16:36.","DSpace SAF Submission Ingestion Package generated from Vireo submission #16967 on 2022-01-12 at 12:55:22","Made available in DSpace on 2022-01-12T22:35:18Z (GMT). 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