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Updated: Feb 8, 2026

An Engineered Split-TET2 Enzyme for Chemical-inducible DNA Hydroxymethylation and Epigenetic Remodeling
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Progress in Epigenetics of Depression.

Catherine J Peña1, Eric J Nestler1

  • 1Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Progress in Molecular Biology and Translational Science
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Summary

Epigenetic factors like DNA methylation and noncoding RNAs are linked to depression. Emerging technologies may offer targeted treatments for this complex psychiatric syndrome.

Keywords:
DNA methylationdepressionepigenetic mechanismshistone modificationsnoncoding RNAs

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Area of Science:

  • Psychiatry
  • Neuroscience
  • Genetics

Background:

  • Depression is a widespread and intricate psychiatric disorder.
  • Epigenetic mechanisms, including DNA methylation, histone modifications, and noncoding RNAs, play a crucial role in bridging genetic and environmental influences on depression.
  • Research has increasingly identified specific epigenetic alterations associated with depression and stress-induced depression-like behaviors in animal models.

Purpose of the Study:

  • To review the current understanding of epigenetic factors associated with depression.
  • To highlight the link between epigenetic changes and the pathophysiology of depression.
  • To explore the potential of emerging technologies for developing targeted depression therapies.

Main Methods:

  • Literature review focusing on recent studies in epigenetics and depression.
  • Analysis of research linking DNA methylation, histone modifications, histone organization, and noncoding RNAs to depression.
  • Examination of findings from animal models of depression and stress-induced behaviors.

Main Results:

  • Numerous epigenetic modifications, including alterations in DNA methylation, histone organization, and noncoding RNAs, are associated with depression.
  • These epigenetic changes can be observed concurrently with depression and in stress-induced depression-like behaviors.
  • While some epigenetic risks have developmental origins, the focus is on concurrent associations.

Conclusions:

  • Epigenetic mechanisms are integral to the development and manifestation of depression.
  • Emerging technologies show promise for precisely targeting and potentially reversing depression-associated epigenetic modifications.
  • Future therapeutic strategies may involve highly specific interventions aimed at correcting epigenetic dysregulation in depression.