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Chromosome Conformation in Context Taylor, James
Description
Chromosome conformation capture (3C) techniques have revealed many features about the structure of chromatin: Large scale organization into two compartments (A and B), relatively stable partitioning into Topologically Associating Domains (TADs) at the megabase scale, and more dynamic and cell type specific interactions associated with various architectural proteins at the sub-megabase scale (sub-TADs). However, these assays are limited in that they only interrogate interactions between chromatin without any connection to location in the nucleus, and are an ensemble measurement over thousands of cells. Here we use integrated analysis of chromosome conformation capture (Hi-C) data, DamID, and single cell imaging to understand the relationship of chromosome conformation features with a specific nuclear compartment, the periphery. Using a new high-resolution compartment scoring algorithm, we show that the B (or generally less active) compartment corresponds to Lamin Associated Domains (LADs) which are positioned at the nuclear lamina. These regions have a histone modification profile typical of heterochromatin, but are also depleted of the architectural protein CTCF, suggesting their organization is CTCF independent. However within the LADs we find many small regions (less than 25kb) that have low signal for Lamin association and a dramatic change in compartment score. These regions are highly enriched for histone states and DNA binding proteins associated with active elements, and appear to contain both transcription start sites and a large number of putative cis-regulatory modules. This suggests regions much smaller than a stereotypical TAD can be organized into a different nuclear compartment from their surrounding DNA, and that this organization is involved in gene regulation at a distance.
Item Metadata
Title |
Chromosome Conformation in Context
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Creator | |
Publisher |
Banff International Research Station for Mathematical Innovation and Discovery
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Date Issued |
2017-03-30T16:00
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Description |
Chromosome conformation capture (3C) techniques have revealed many
features about the structure of chromatin: Large scale organization
into two compartments (A and B), relatively stable partitioning into
Topologically Associating Domains (TADs) at the megabase scale, and
more dynamic and cell type specific interactions associated with
various architectural proteins at the sub-megabase scale (sub-TADs).
However, these assays are limited in that they only interrogate
interactions between chromatin without any connection to location in
the nucleus, and are an ensemble measurement over thousands of cells.
Here we use integrated analysis of chromosome conformation capture
(Hi-C) data, DamID, and single cell imaging to understand the
relationship of chromosome conformation features with a specific
nuclear compartment, the periphery. Using a new high-resolution
compartment scoring algorithm, we show that the B (or generally less
active) compartment corresponds to Lamin Associated Domains (LADs)
which are positioned at the nuclear lamina. These regions have a
histone modification profile typical of heterochromatin, but are also
depleted of the architectural protein CTCF, suggesting their
organization is CTCF independent. However within the LADs we find many
small regions (less than 25kb) that have low signal for Lamin
association and a dramatic change in compartment score. These regions
are highly enriched for histone states and DNA binding proteins
associated with active elements, and appear to contain both
transcription start sites and a large number of putative
cis-regulatory modules. This suggests regions much smaller than a
stereotypical TAD can be organized into a different nuclear
compartment from their surrounding DNA, and that this organization is
involved in gene regulation at a distance.
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Extent |
24 minutes
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Subject | |
Type | |
File Format |
video/mp4
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Language |
eng
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Notes |
Author affiliation: Johns Hopkins University
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Series | |
Date Available |
2017-09-27
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0355793
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URI | |
Affiliation | |
Peer Review Status |
Unreviewed
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Scholarly Level |
Faculty
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International