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Status |
Public on May 24, 2013 |
Title |
Architectural protein subclasses shape 3-D organization of genomes during lineage commitment |
Organism |
Mus musculus |
Experiment type |
Genome variation profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Understanding the topological configurations of chromatin can reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3-D interactions that undergo marked reorganization at the sub-Mb scale during differentiation. Distinct combinations of CTCF, Mediator, and cohesin show widespread enrichment in architecture at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant sub-domains. Conversely, Mediator/cohesin together with pioneer factors bridge short-range enhancer-promoter interactions within and between larger sub-domains. Knockdown of Smc1 or Med12 in ES cells results in disruption of spatial architecture and down-regulation of genes found in cohesin-mediated interactions. We conclude that cell type-specific chromatin organization occurs at the sub-Mb scale and that architectural proteins shape the genome in hierarchical length scales.
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Overall design |
Analysis of higher-order chromatin chromatin architecture in mouse ES cells and ES-derived NPCs. Analysis of CTCF and Smc1 occupied sites in ES-derived NPCs.
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Contributor(s) |
Phillips-Cremins JE |
Citation(s) |
23706625 |
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Submission date |
Mar 01, 2012 |
Last update date |
May 15, 2019 |
Contact name |
Jennifer Elizabeth Phillips-Cremins |
E-mail(s) |
Jennifer.Phillips-Cremins@umassmed.edu
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Organization name |
University of Massachusetts Medical School and Emory University
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Department |
Program in Systems Biology and Department of Biology
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Lab |
Job Dekker Laboratory and Victor Corces Laboratory
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Street address |
364 Plantation Street
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City |
Worcester |
State/province |
MA |
ZIP/Postal code |
01605 |
Country |
USA |
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Platforms (2) |
GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (7)
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Relations |
SRA |
SRP011234 |
BioProject |
PRJNA152875 |