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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
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Chromatin remodeling inactivates activity genes and regulates neural coding.
Yue Yang1, Tomoko Yamada1, Kelly K Hill1,2
1Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
Science (New York, N.Y.)
|July 16, 2016
Summary
The nucleosome remodeling and deacetylase (NuRD) complex inactivates activity-dependent genes in brain development. This epigenetic mechanism regulates neuronal connectivity and sensorimotor processing.
Area of Science:
- Neuroscience
- Epigenetics
- Molecular Biology
Background:
- Activity-dependent transcription is crucial for neuronal connectivity.
- Mechanisms of inactivating these genes are not well understood.
Purpose of the Study:
- To investigate the role of the NuRD complex in inactivating activity-dependent genes.
- To understand how this process impacts neuronal development and function.
Main Methods:
- Genome-wide analyses in mouse cerebellum.
- Purification of translating messenger RNAs (Sync-TRAP).
- Conditional knockout of the Chd4 subunit of NuRD.
- Imaging in behaving mice.
Main Results:
- NuRD complex deposits H2A.z at promoters of activity-dependent genes, causing inactivation.
- Chd4 knockout impairs gene inactivation during dendrite pruning.
- Chd4 knockout or altered gene expression disrupts dendrite pruning.
- Mice lacking Chd4 show hyperresponsive neurons.
Conclusions:
- NuRD complex provides an epigenetic mechanism for inactivating activity-dependent transcription.
- This mechanism is essential for regulating dendrite patterning.
- It also plays a role in sensorimotor encoding in the brain.
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