Corticosterone dynamically regulates retrotransposable element expression in the rat hippocampus and C6 cells

Area of Science:

• Neuroscience
• Epigenetics
• Molecular Biology

Background:

• The hippocampus is a brain region crucial for learning and memory, highly sensitive to stress.
• Stress impacts hippocampal epigenetic marks, influencing gene expression related to stress responses.
• Histone H3 lysine 9 trimethylation (H3K9me3) changes are observed in the hippocampus following acute stress, particularly at transposable elements.

Purpose of the Study:

• To investigate the effect of acute glucocorticoid treatment on hippocampal H3K9me3 levels.
• To determine the specific localization of H3K9me3 changes at different types of transposable elements.
• To assess the relationship between H3K9me3 modifications and the transcriptional activity of transposable elements.

Main Methods:

• Acute glucocorticoid administration to rodents.
• Global and targeted analysis of histone H3K9 trimethylation (H3K9me3) in hippocampal tissue.
• Quantification of transcript abundance for specific transposable elements (B2 SINEs, IAPE).

Main Results:

• Acute glucocorticoid treatment induced global H3K9me3 changes in the hippocampus.
• H3K9me3 was significantly decreased at B2 short interspersed nuclear elements (SINEs) but not at intracisternal-A particle (IAP) endogenous retroviruses.
• Reduced H3K9me3 at B2 elements correlated with increased their transcript abundance.

Conclusions:

• Acute glucocorticoids can mobilize transposable elements through epigenetic modifications (unmasking).
• These findings, consistent with stress-induced changes, suggest transposable elements are dynamically regulated by stress and glucocorticoids.
• Mobile elements in the hippocampus may function as novel regulators in response to stress and glucocorticoid signaling.