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Related Concept Videos

Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...
Maintenance of the ES Cell State01:14

Maintenance of the ES Cell State

The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Combinatorial Gene Control02:33

Combinatorial Gene Control

Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
Chromosome Replication02:31

Chromosome Replication

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 of...

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Chromosome Replicating Timing Combined with Fluorescent In situ Hybridization
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Published on: December 10, 2012

Replication timing: a fingerprint for cell identity and pluripotency.

Tyrone Ryba1, Ichiro Hiratani, Takayo Sasaki

  • 1Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America.

Plos Computational Biology
|October 27, 2011
PubMed
Summary

Replication timing fingerprints offer a novel epigenetic method for classifying cell types, including stem cells and cancer subtypes. This approach accurately identifies cells and reveals epigenetic barriers to reprogramming.

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Area of Science:

  • Epigenetics
  • Genomics
  • Cell Biology

Background:

  • Epigenetic profiling is crucial for classifying cell types, differentiation stages, and cancers.
  • Current methods focus on local chromatin features, demanding extensive analysis for genome-wide data.
  • Replication timing is a stable, cell type-specific epigenetic feature, easily analyzed genome-wide at the megabase level.

Purpose of the Study:

  • To develop a cell classification method based on replication timing profiles.
  • To identify unique "replication timing fingerprints" for various cell types.
  • To investigate replication timing's role in pluripotency and differentiation.

Main Methods:

  • Utilized 67 replication profiles from 34 mouse and human cell lines and tissues.
  • Employed a Monte-Carlo approach to identify conserved replication profile features.
  • Applied a k-nearest neighbor algorithm for cell type prediction.
  • Validated the method on independent replication-timing profiles.

Main Results:

  • Developed and validated a cell classification method using replication timing fingerprints, achieving 100% accuracy on 67 profiles.
  • Identified pluripotency fingerprints in human and mouse cells, revealing potential epigenetic barriers to reprogramming.
  • Observed consistent late replication of the Hist1 cluster during differentiation, linked to histone gene downregulation and chromatin compaction.

Conclusions:

  • Replication fingerprints provide a comprehensive and accurate method for cell characterization.
  • This approach can identify cell type-specific epigenetic organization and barriers to reprogramming.
  • Replication timing analysis offers a powerful tool for understanding cellular identity and epigenetic regulation.