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The SETD6 Methyltransferase Plays an Essential Role in Hippocampus-Dependent Memory Formation
William M Webb1, Ashleigh B Irwin1, Mark E Pepin2
1Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, Alabama.
Biological Psychiatry
|August 6, 2019
Summary
The N-lysine methyltransferase SETD6 is crucial for long-term memory formation. Its knockdown impairs memory consolidation by affecting gene expression and neuronal structure in the hippocampus.
Area of Science:
- Neuroscience
- Epigenetics
- Molecular Biology
Background:
- Epigenetic mechanisms regulate hippocampus-dependent memory.
- SETD6, an N-lysine methyltransferase, is implicated in activating nuclear factor-κB RELA (RELA) as an epigenetic recruiter.
Purpose of the Study:
- To investigate the role of SETD6 in the epigenetic control of long-term memory.
- To test the hypothesis that SETD6 is a key player in memory formation.
Main Methods:
- Short interfering RNA-mediated knockdown of Setd6 in the rat dorsal hippocampus.
- Utilized molecular, biochemical, imaging, electrophysiological, and behavioral experiments.
Main Results:
- SETD6 is essential for memory-related RELA methylation at lysine 310 and H3K9me2 increases in the dorsal hippocampus.
- SETD6 knockdown disrupted memory consolidation, altered gene expression, and affected spine morphology.
Conclusions:
- SETD6 plays a critical role in hippocampus-dependent memory formation.
- SETD6 may initiate H3K9me2 changes during memory consolidation.
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