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Related Concept Videos

Chromatin Modification in iPS Cells01:32

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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.
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Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
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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...
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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
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Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
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Reprogramming of DNA methylation at NEUROD2-bound sequences during cortical neuron differentiation.

Maria A Hahn1, Seung-Gi Jin2, Arthur X Li3

  • 1Department of Surgery, City of Hope, Duarte, CA 91010, USA.

Science Advances
|November 5, 2019
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Summary

DNA methylation changes during neurogenesis are revealed. NEUROD2 and TET2 mediate DNA demethylation at enhancers, crucial for neuronal development and gene regulation.

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Immunostaining for DNA Modifications: Computational Analysis of Confocal Images
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Area of Science:

  • Neuroscience
  • Epigenetics
  • Developmental Biology

Background:

  • The role of DNA methylation in neurogenesis is not fully understood.
  • Understanding epigenetic modifications is key to deciphering neuronal development.

Purpose of the Study:

  • To investigate DNA methylation patterns during in vivo neurogenesis.
  • To identify the molecular mechanisms driving these epigenetic changes in developing neurons.

Main Methods:

  • Whole-genome bisulfite sequencing (WGBS) was employed to analyze DNA cytosine modifications.
  • Analysis was performed on differentiating neurons and progenitors from mouse embryonic brains.
  • Interactions between transcription factors and epigenetic modifiers were examined.

Main Results:

  • Localized DNA hypomethylation was prevalent, particularly at enhancers of neuron-specific genes.
  • Hypomethylated regions overlapped significantly with binding sites of the neuronal transcription factor NEUROD2.
  • The enzyme ten-eleven translocation 2 (TET2) was found to interact with NEUROD2, facilitating demethylation via 5-hydroxymethylcytosine accumulation.

Conclusions:

  • NEUROD2 and TET2 play a critical role in the dynamic DNA demethylation during neurogenesis.
  • This epigenetic reprogramming is essential for the upregulation of genes vital for neuronal differentiation.
  • The findings elucidate a novel mechanism of epigenetic regulation in the developing brain.