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Behavioral changes in response to stressful stimuli
can be controlled via adaptive epigenetic changes in
neuronal gene expression. Researchers indicate a
role for the transcriptional corepressor
Lysine-Specific Demethylase 1 (LSD1) and its
dominant-negative splicing isoform neuroLSD1, in the
modulation of emotional behavior.
In mouse hippocampus, researchers show that LSD1 and
neuroLSD1 can interact with transcription factor
serum response factor (SRF) and set the chromatin
state of SRF-targeted genes early growth response 1
(egr1) and c-fos.
Deletion or reduction of neuroLSD1 in mutant mice
translates into decreased levels of activating
histone marks at egr1 and c-fos promoters, dampening
their psychosocial stress-induced transcription and
resulting in low anxiety-like behavior.
Administration of suberoylanilide hydroxamine to
neuroLSD1KO mice reactivates egr1 and c-fos
transcription and restores the behavioral phenotype.
These findings indicate that LSD1 is a molecular
transducer of stressful stimuli as well as a
stress-response modifier. Indeed, LSD1 expression
itself is increased acutely at both the
transcriptional and splicing levels by psychosocial
stress, suggesting that LSD1 is involved in the
adaptive response to stress.
For more information
LSD1 modulates stress-evoked transcription of
immediate early genes and emotional behavior.
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