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Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

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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.
X-chromosome...
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Epigenetic Regulation01:46

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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Phase II Reactions: Methylation Reactions01:17

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Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
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Spreading of Chromatin Modifications02:25

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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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Histone Modification02:32

Histone Modification

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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
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Immunostaining for DNA Modifications: Computational Analysis of Confocal Images
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TET-mediated active DNA demethylation: mechanism, function and beyond.

Xiaoji Wu1,2,3,4,5, Yi Zhang1,2,3,4

  • 1Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.

Nature Reviews. Genetics
|May 31, 2017
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Active DNA demethylation in mammals involves TET enzymes and TDG, reversing 5-methylcytosine (5mC) through oxidation and repair. Recent advances reveal mechanisms, regulation, and biological roles of this crucial epigenetic process.

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Area of Science:

  • Epigenetics
  • Molecular Biology
  • Biochemistry

Background:

  • DNA methylation (5mC) is a key epigenetic mark.
  • Active reversal of 5mC is essential for cellular function.
  • TET dioxygenases and TDG are central to active DNA demethylation.

Purpose of the Study:

  • To review recent advances in active DNA demethylation.
  • To elucidate the mechanisms of TET and TDG in demethylation.
  • To highlight the biological functions and unanswered questions in the field.

Main Methods:

  • Biochemical studies
  • Structural biology
  • Mapping and tracing of oxidized 5mC forms

Main Results:

  • Mechanistic insights into TET and TDG functions.
  • Identification of regulatory mechanisms for active demethylation.
  • Understanding the biological roles of oxidized 5mC intermediates.

Conclusions:

  • Active DNA demethylation is a complex, regulated process.
  • Technological advances facilitate deeper understanding.
  • Further research is needed to address key unanswered questions.