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Updated: Aug 31, 2025

Formaldehyde-assisted Isolation of Regulatory Elements to Measure Chromatin Accessibility in Mammalian Cells
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Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements.

Ignacio L Ibarra1,2,3, Vikram S Ratnu4, Lucia Gordillo2,4

  • 1Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.

Molecular Systems Biology
|August 23, 2022
PubMed
Summary

Brain-derived neurotrophic factor (BDNF) shapes neuronal gene expression by opening chromatin, influencing synaptic plasticity and neurodevelopmental genes. This study reveals BDNF-specific genomic regulatory programs in neurons.

Keywords:
enhancersgene expressionneuronal stimulationpost-mitotic neuronstranscription factors

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Area of Science:

  • Neuroscience
  • Genomics
  • Molecular Biology

Background:

  • Brain-derived neurotrophic factor (BDNF) is vital for neuronal functions like survival, differentiation, and memory.
  • The precise role of BDNF in regulating chromatin accessibility and gene expression remains largely unexplored.

Purpose of the Study:

  • To elucidate the specific chromatin regulatory mechanisms underlying BDNF-induced gene expression programs in neurons.
  • To identify early molecular events and transcription factors involved in BDNF-mediated chromatin remodeling.

Main Methods:

  • Temporal profiling of chromatin accessibility and gene transcription in mouse primary cortical neurons.
  • Comparative genomic analysis comparing BDNF stimulation with depolarization (KCl).
  • Validation in human induced pluripotent stem cell (iPSC)-derived neurons.

Main Results:

  • BDNF stimulation initiates early enhancer activation, with Fos protein pioneering chromatin opening.
  • Cooperation between Fos and other transcription factors (Homeobox, EGRs, CTCF) drives transcription.
  • BDNF-regulated accessible regions influence exon usage in neurodevelopmental genes and heritability of neuronal traits.

Conclusions:

  • BDNF orchestrates specific genome regulatory programs essential for neuronal function and plasticity.
  • This work provides a comprehensive view of BDNF-mediated genomic features, linking chromatin regulation to neurodevelopmental and complex neuronal traits.