Show simple item record

dc.contributor.advisorJob Dekker
dc.contributor.authorAbramo, Kristin N.
dc.date2022-08-11T08:08:38.000
dc.date.accessioned2022-08-23T16:02:32Z
dc.date.available2022-08-23T16:02:32Z
dc.date.issued2020-07-28
dc.date.submitted2020-09-01
dc.identifier.doi10.13028/a9gd-gw44
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31325
dc.description.abstractFollowing the discovery of the one-dimensional sequence of human DNA, much focus has been directed on microscopy and molecular techniques to learn about the spatial organization of chromatin in a 3D cell. The development of these powerful tools has enabled high-resolution, genome-wide analysis of chromosome structure under many different conditions. In this thesis, I focus on how the organization of interphase chromatin is established and maintained following mitosis. Mitotic chromosomes are folded into helical loop arrays creating short and condensed chromosomes, while interphase chromosomes are decondensed and folded into a number of structures at different length scales ranging from loops between CTCF sites, enhancers and promoters to topologically associating domains (TADs), and larger compartments. While the chromatin organization at these two very different states is well defined, the transition from a mitotic to interphase chromatin state is not well understood. The aim of this thesis is to determine how interphase chromatin is organized following mitotic chromosome decondensation and to interrogate factors potentially responsible for driving the transition. First, I determine the temporal order with which CTCF-loops, TADs, and compartments reform as cells exit mitosis, revealing a unique structure at the anaphase-telophase transition never observed before. Second, I test the role of transcription in reformation of 3D chromosome structure and show that active transcription is not required for the formation of most interphase chromatin features; instead, I propose that transcription relies on the proper formation of these structures. Finally, I show that RNA in the interphase nucleus can be degraded with only slight consequences on the overall chromatin organization, suggesting that once interphase chromatin structures are achieved, the structures are stable and RNA is only required to reduce the mixing of active and inactive compartments. Together, these studies further our understanding of how interphase structures form, how these structures relate to functional activities of the interphase cell, and the stability of chromatin structures over time.
dc.language.isoen_US
dc.rightsLicensed under a Creative Commons license
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectchromatin
dc.subjectHi-C
dc.subjecttranscription
dc.subjectRNA
dc.subjecttelophase
dc.subjectkinetics
dc.subjectcell cycle
dc.subjectmitosis
dc.subjectinterphase
dc.subjectchromosome conformation capture
dc.subjectCTCF
dc.subjectcondensin
dc.subjectcohesin
dc.subjectTAD
dc.subjecttopologically associated domain
dc.subjectloop extrusion
dc.subjectmicrophase separation
dc.subjectNCAPH
dc.subjectRad21
dc.subjectNCAPH2
dc.subjectsynchronization
dc.subjectG1 entry
dc.subjecttriptolide
dc.subjectDRB
dc.subjectRNase A
dc.subjectBioinformatics
dc.subjectCell Biology
dc.subjectComputational Biology
dc.subjectGenomics
dc.subjectLaboratory and Basic Science Research
dc.subjectMolecular Biology
dc.subjectMolecular Genetics
dc.subjectSystems Biology
dc.titleBuilding the Interphase Nucleus: A study on the kinetics of 3D chromosome formation, temporal relation to active transcription, and the role of nuclear RNAs
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2108&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/1099
dc.legacy.embargo2020-09-01T00:00:00-07:00
dc.identifier.contextkey19212655
refterms.dateFOA2022-08-25T04:30:33Z
html.description.abstract<p>Following the discovery of the one-dimensional sequence of human DNA, much focus has been directed on microscopy and molecular techniques to learn about the spatial organization of chromatin in a 3D cell. The development of these powerful tools has enabled high-resolution, genome-wide analysis of chromosome structure under many different conditions. In this thesis, I focus on how the organization of interphase chromatin is established and maintained following mitosis. Mitotic chromosomes are folded into helical loop arrays creating short and condensed chromosomes, while interphase chromosomes are decondensed and folded into a number of structures at different length scales ranging from loops between CTCF sites, enhancers and promoters to topologically associating domains (TADs), and larger compartments. While the chromatin organization at these two very different states is well defined, the transition from a mitotic to interphase chromatin state is not well understood.</p> <p>The aim of this thesis is to determine how interphase chromatin is organized following mitotic chromosome decondensation and to interrogate factors potentially responsible for driving the transition. First, I determine the temporal order with which CTCF-loops, TADs, and compartments reform as cells exit mitosis, revealing a unique structure at the anaphase-telophase transition never observed before. Second, I test the role of transcription in reformation of 3D chromosome structure and show that active transcription is not required for the formation of most interphase chromatin features; instead, I propose that transcription relies on the proper formation of these structures. Finally, I show that RNA in the interphase nucleus can be degraded with only slight consequences on the overall chromatin organization, suggesting that once interphase chromatin structures are achieved, the structures are stable and RNA is only required to reduce the mixing of active and inactive compartments. Together, these studies further our understanding of how interphase structures form, how these structures relate to functional activities of the interphase cell, and the stability of chromatin structures over time.</p>
dc.identifier.submissionpathgsbs_diss/1099
dc.contributor.departmentProgram in Systems Biology
dc.description.thesisprogramInterdisciplinary Graduate Program
dc.identifier.orcid0000-0003-4854-8684


Files in this item

Thumbnail
Name:
Abramo_Thesis_final.pdf
Size:
10.92Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

Licensed under a Creative Commons license
Except where otherwise noted, this item's license is described as Licensed under a Creative Commons license