University of Illinois Urbana-Champaign

Genomic and microscopic dissection of large-scale chromatin compaction

Gholamalamdari, Omid

Content Files
GHOLAMALAMDARI-DISSERTATION-2021.pdf

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https://hdl.handle.net/2142/113207

Description

Title
Genomic and microscopic dissection of large-scale chromatin compaction
Author(s)
Gholamalamdari, Omid
Issue Date
2021-07-15
Director of Research (if dissertation) or Advisor (if thesis)
Belmont, Andrew S
Doctoral Committee Chair(s)
Belmont, Andrew S
Committee Member(s)
  • Brieher, William M
  • Freeman, Brian C
  • Sinha, Saurabh
Department of Study
Cell & Developmental Biology
Discipline
Cell and Developmental Biology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2022-01-12T22:35:18Z
Keyword(s)
  • chromatin structure
  • compaction
  • genome organization
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.
Graduation Semester
2021-08
Type of Resource
Thesis
Permalink
http://hdl.handle.net/2142/113207
Copyright and License Information
Copyright 2021 Omid Gholamalamdari

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