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Insights into the role of nucleosomal DNA folding on chromatin fiber properties

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TitleInfo
Title
Insights into the role of nucleosomal DNA folding on chromatin fiber properties
Name (type = personal)
NamePart (type = family)
Todolli
NamePart (type = given)
Stefjord
NamePart (type = date)
1988-
DisplayForm
Stefjord Todolli
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Olson
NamePart (type = given)
Wilma K
DisplayForm
Wilma K Olson
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Case
NamePart (type = given)
David A
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David A Case
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Khare
NamePart (type = given)
Sagar
DisplayForm
Sagar Khare
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Studitsky
NamePart (type = given)
Vasily M
DisplayForm
Vasily M Studitsky
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2019
DateOther (qualifier = exact); (type = degree)
2019-01
CopyrightDate (encoding = w3cdtf)
2019
Place
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xx
Language
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eng
Abstract (type = abstract)
DNA in eukaryotic cell nuclei is packaged in a highly compact, yet dynamic chromatin structure that provides a regulatory mechanism for many biological processes, such as gene expression. The basic packaging unit of chromatin is the nucleosome, which consists of ~1.7 turns of DNA wrapped around an octamer core of histone proteins (H3, H4, H2A, H2B). Chains of nucleosome-decorated DNA, which resemble beads on a string, fold into a higher-order arrangement, often referred to as the 30-nm fiber. However, the structure of this fiber remains poorly understood, despite decades of research. Many proposed models for the 3D organization of the nucleosomes and intervening DNA in chromatin vary quite significantly, and the very existence and relevance of a 30-nm structure in vivo has been questioned.
An analysis of the available high-resolution nucleosome structures shows subtle, yet significant differences in DNA wrapping around the histone core. Monte Carlo simulations of regular nucleosome arrays generated using a meso-scale representation of DNA suggest that these local differences can lead to large changes in global nucleosome arrangements, comparable to the effect of changes in nucleosome spacing by ~2–3 base pairs. Our results suggest that a regular nucleosome array with a 177-base-pair (bp) repeat can display a loose three-stack or a more compact two-stack arrangement, on average, depending on the DNA wrapping profile of the nucleosome. These findings imply a very dynamic chromatin fiber with a multitude of mechanisms to control its folding.
Using this meso-scale model, we have studied the role of chromatin fiber architecture and histone tails on chromatin compaction and long-range communication in constructs containing 177-bp repeats. Our predictions for chromatin fibers with a loose three-stack nucleosome arrangement can qualitatively account for experimental data from in vitro assays of enhancer-promoter communication (EPC) under physiologically-relevant conditions. On the other hand, fibers that display a two-stack arrangement are in better agreement with sedimentation velocity experiments performed under a different set of ionic conditions. Removal of histone tails diminishes EPC efficiency, and our simulations predict that H3/H4 tail removal has the biggest impact, in agreement with in vitro experiments.
Subject (authority = RUETD)
Topic
Quantitative Biomedicine
Subject (authority = ETD-LCSH)
Topic
Chromatin
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9525
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (101 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Stefjord Todolli
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-srzs-a748
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Todolli
GivenName
Stefjord
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-01-11 16:14:54
AssociatedEntity
Name
Stefjord Todolli
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
Type
Embargo
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-01-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2021-01-30
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after January 30th, 2021.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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