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dc.contributor.advisorOliver J. Rando, M.D., Ph.D.
dc.contributor.authorHsieh, Tsung-Han S.
dc.date2022-08-11T08:08:46.000
dc.date.accessioned2022-08-23T16:07:37Z
dc.date.available2022-08-23T16:07:37Z
dc.date.issued2017-05-15
dc.date.submitted2017-06-24
dc.identifier.doi10.13028/M2MX01
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32283
dc.description.abstractChromatin packages eukaryotic genomes via a hierarchical series of folding steps, encrypting multiple layers of epigenetic information, which are capable of regulating nuclear transactions in response to complex signals in environment. Besides the 1-dimensinal chromatin landscape such as nucleosome positioning and histone modifications, little is known about the secondary chromatin structures and their functional consequences related to transcriptional regulation and DNA replication. The family of chromosomal conformation capture (3C) assays has revolutionized our understanding of large-scale chromosome folding with the ability to measure relative interaction probability between genomic loci in vivo. However, the suboptimal resolution of the typical 3C techniques leaves the levels of nucleosome interactions or 30 nm structures inaccessible, and also restricts their applicability to study gene level of chromatin folding in small genome organisms such as yeasts, worm, and plants. To uncover the “blind spot” of chromatin organization, I developed an innovative method called Micro-C and an improved protocol, Micro-C XL, which enable to map chromatin structures at all range of scale from single nucleosome to the entire genome. Several fine-scale aspects of chromatin folding in budding and fission yeasts have been identified by Micro-C, including histone tail-mediated tri-/tetra-nucleosome stackings, gene crumples/globules, and chromosomally-interacting domains (CIDs). CIDs are spatially demarcated by the boundaries, which are colocalized with the promoters of actively transcribed genes and histone marks for active transcription or turnover. The levels of chromatin compaction are regulated via transcription-dependent or transcription-independent manner – either the perturbations of transcription or the mutations of chromatin regulators strongly affect the global chromatin folding. Taken together, Micro-C further reveals chromatin folding behaviors below the sub-kilobase scale and opens an avenue to study chromatin organization in many biological systems.
dc.language.isoen_US
dc.relation.urlhttps://goo.gl/riWJW4
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectChromatin
dc.subjectNucleosome
dc.subject3D genome
dc.subjectHistone modifications
dc.subjectBiotechnology
dc.subjectGenetics
dc.subjectGenomics
dc.subjectMolecular Biology
dc.titleThree-dimensional Folding of Eukaryotic Genomes
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1907&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/903
dc.legacy.embargo2017-06-24T00:00:00-07:00
dc.identifier.contextkey10347751
refterms.dateFOA2022-08-27T04:55:18Z
html.description.abstract<p>Chromatin packages eukaryotic genomes via a hierarchical series of folding steps, encrypting multiple layers of epigenetic information, which are capable of regulating nuclear transactions in response to complex signals in environment. Besides the 1-dimensinal chromatin landscape such as nucleosome positioning and histone modifications, little is known about the secondary chromatin structures and their functional consequences related to transcriptional regulation and DNA replication. The family of chromosomal conformation capture (3C) assays has revolutionized our understanding of large-scale chromosome folding with the ability to measure relative interaction probability between genomic loci <em>in vivo</em>. However, the suboptimal resolution of the typical 3C techniques leaves the levels of nucleosome interactions or 30 nm structures inaccessible, and also restricts their applicability to study gene level of chromatin folding in small genome organisms such as yeasts, worm, and plants. To uncover the “blind spot” of chromatin organization, I developed an innovative method called Micro-C and an improved protocol, Micro-C XL, which enable to map chromatin structures at all range of scale from single nucleosome to the entire genome. Several fine-scale aspects of chromatin folding in budding and fission yeasts have been identified by Micro-C, including histone tail-mediated tri-/tetra-nucleosome stackings, gene crumples/globules, and chromosomally-interacting domains (CIDs). CIDs are spatially demarcated by the boundaries, which are colocalized with the promoters of actively transcribed genes and histone marks for active transcription or turnover. The levels of chromatin compaction are regulated via transcription-dependent or transcription-independent manner – either the perturbations of transcription or the mutations of chromatin regulators strongly affect the global chromatin folding. Taken together, Micro-C further reveals chromatin folding behaviors below the sub-kilobase scale and opens an avenue to study chromatin organization in many biological systems.</p>
dc.identifier.submissionpathgsbs_diss/903
dc.contributor.departmentBiochemistry and Molecular Pharmacology
dc.description.thesisprogramInterdisciplinary Graduate Program
dc.identifier.orcid0000-0003-2094-0772


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