Architecture of interphase chromosomes

Placeholder Show Content

Abstract/Contents

Abstract
How DNA folds within nuclei and chromosomes is a great unanswered question in biology. A technology which employs chemical cross-linking of chromatin followed by restriction digestion, proximity ligation, and high-throughput DNA sequencing (Hi-C) has revealed regions of chromatin more likely to interact with themselves than with their neighbors, known as "topologically associating domains" (TADs), separated by regions of little or no such interaction. TADs regulate gene expression by modulating enhancer-promoter communication, but the physical nature of TADs remains unresolved. I have found that TADs and the regions between them correspond to the bands and interbands of the polytene chromosomes of Drosophila melanogaster. Polytene TADs are conserved with diploid TADs, identifying the polytene band-interband pattern as the principle underlying axial chromosome organization. Based on direct measurements from polytene chromosomes, TADs represent a stable state of chromatin condensation up to 30-fold more condensed than a fully extended, "beads-on-a-string" chromatin fiber. Hi-C at sub-kilobase resolution revealed the location of Drosophila chromatin loops, which commonly reside within TADs and are bound by the polycomb group protein, Polycomb. These loops are associated with gene repression and are located at some of the most important developmentally regulated genes. By combining molecular analysis with direct observation from cytology, the architecture of interphase chromosomes is revealed.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2016
Issuance monographic
Language English

Creators/Contributors

Associated with Eagen, Kyle Patrick
Associated with Stanford University, Biophysics Program.
Primary advisor Kornberg, Roger D
Thesis advisor Kornberg, Roger D
Thesis advisor Weis, William I
Thesis advisor Wysocka, Joanna, Ph. D
Advisor Weis, William I
Advisor Wysocka, Joanna, Ph. D

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Kyle Patrick Eagen.
Note Submitted to the Program in Biophysics.
Thesis Thesis (Ph.D.)--Stanford University, 2016.
Location electronic resource

Access conditions

Copyright
© 2016 by Kyle Patrick Eagen
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

Also listed in

Loading usage metrics...