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3D Multicolor DNA FISH Tool to Study Nuclear Architecture in Human Primary Cells
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Published on: January 25, 2020

Identical cells with different 3D genomes; cause and consequences?

Peter H L Krijger1, Wouter de Laat

  • 1Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Urecht, The Netherlands.

Current Opinion in Genetics & Development
|February 19, 2013
PubMed
Summary

Mammalian genomes fold into domains to regulate gene expression. Cell-specific DNA contacts, explained by the "dog-on-a-lead" model, lead to varied gene expression even in identical cells.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Epigenetics

Background:

  • The mammalian genome is organized into topological domains, crucial for regulating gene expression.
  • Gene expression control involves spatial arrangement of DNA elements like enhancers and promoters.
  • Cell-specific, long-range DNA contacts occur beyond established topological domains.

Purpose of the Study:

  • To propose a model explaining cell-specific remote DNA contacts.
  • To understand the principles and consequences of these dynamic genomic interactions.
  • To investigate how cell-specific genome topologies influence gene expression variability.

Main Methods:

  • Development of the "dog-on-a-lead" model.
  • Theoretical analysis of genome folding and long-range interactions.
  • Computational modeling of cell-specific chromatin dynamics.

Main Results:

  • The "dog-on-a-lead" model provides a framework for understanding remote DNA contacts.
  • Cell-specific genome topologies are a plausible mechanism for gene expression variation.
  • Identical cells can exhibit distinct gene expression patterns due to unique genome folding.

Conclusions:

  • Cell-specific genome topology is a key factor in generating cell-to-cell expression heterogeneity.
  • The proposed model offers insights into the functional significance of dynamic genome organization.
  • Understanding these principles is crucial for fields ranging from developmental biology to disease research.