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Related Concept Videos

Chromosome Replication02:31

Chromosome Replication

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Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
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In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
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A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
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Genome-wide Determination of Mammalian Replication Timing by DNA Content Measurement
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Structural organization of human replication timing domains.

Rasha E Boulos1, Guénola Drillon1, Françoise Argoul1

  • 1Université de Lyon, F-69000 Lyon, France; Laboratoire de Physique, CNRS UMR5672, Ecole Normale Supérieure de Lyon, F-69007 Lyon, France.

FEBS Letters
|April 28, 2015
PubMed
Summary

Replication timing is controlled by local epigenetics and 3D chromatin structure. New models show U-shaped mean replication timing domains initiated by master origins, linking chromatin organization to cell differentiation.

Keywords:
Chromatin conformationChromatin statesEquilibrium and fractal globule modelsLamina-associated domainsReplication timing domainsTopologically associated domains

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Area of Science:

  • Genomics
  • Epigenetics
  • Cell Biology

Background:

  • Replication origin usage flexibility is influenced by epigenetic modifications and 3D chromatin architecture.
  • Previous models proposed distinct early and late replicating regions based on chromatin state.

Purpose of the Study:

  • To review recent findings on the link between replication domains and chromatin structural domains in human cells.
  • To reconcile existing models of replication timing with new data on chromatin organization.

Main Methods:

  • Analysis of genome-wide epigenetic modification data.
  • Examination of mean replication timing (MRT) profiles.
  • Integration of chromosome conformation capture data.

Main Results:

  • Replication domains are linked to chromatin structural domains (TADs, LADs) in pluripotent and differentiated human cells.
  • A U-shaped MRT domain model is proposed, with replication initiating from master origins in open chromatin.
  • Replication propagates from master origins towards the domain center via origin firing cascades.

Conclusions:

  • Epigenetic landscape and 3D chromatin architecture regulate replication origin usage.
  • The proposed U-shaped MRT domain model integrates previous findings and explains replication timing regulation.
  • Chromatin reorganization underlies pluripotency loss and cell differentiation.