Journal
SCIENCE SIGNALING
Volume 12, Issue 588, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aaw9277
Keywords
-
Categories
Funding
- NIH [MH097909]
- Evelyn F. McKnight Brain Institute at UAB
- UAB Neuroscience Behavior Assessment Core [P30 NS47466]
- NIH Institutional Training grant [NS061788]
Ask authors/readers for more resources
Histone methylation is critical for the formation and maintenance of long-term memories. Long noncoding RNAs (lncRNAs) are regulators of histone methyltransferases and other chromatin-modifying enzymes (CMEs), thereby epigenetically modifying gene expression. Here, we investigated how the lncRNA NEAT1 may epigenetically contribute to hippocampus-dependent, long-term memory formation using a combination of transcriptomics, RNA-binding protein immunoprecipitation, CRISPR-mediated gene activation (CRISPRa), and behavioral approaches. Knockdown of the lncRNA Neat1 revealed widespread changes in gene transcription, as well as perturbations of histone 3 lysine 9 dimethylation (H3K9me2), a repressive histone modification mark that was increased in the hippocampus of aging rodents. We identified a NEAT1-dependent mechanism of transcriptional repression by H3K9me2 at the c-Fos promoter, corresponding with observed changes in c-Fos mRNA expression. Overexpression of hippocampal NEAT1 using CRISPRa was sufficient to impair memory formation in young adult mice, recapitulating observed memory deficits in old adult mice, whereas knocking down NEAT1 in both young and old adult mice improved behavior test-associated memory. These results suggest that the lncRNA NEAT1 is an epigenetic suppressor of hippocampus-dependent, long-term memory formation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available