期刊
CELL REPORTS
卷 38, 期 12, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2022.110546
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类别
资金
- Brain and Behavioral Research Foundation (NARSAD Independent Investigator Award)
- NIH [R01MH109588, 1R21MH103812]
- ARC [DP180102998, DP190100234]
- NSFC [82171517, 82001421]
- University of Queensland
In this study, RNA capture-seq was used to identify a large population of lncRNAs expressed in the infralimbic prefrontal cortex of adult male mice after fear-related learning. A specific lncRNA called ADRAM was discovered, which acts as both a scaffold and a guide to regulate the expression of memory-associated genes and is required for fear extinction memory.
Here, we used RNA capture-seq to identify a large population of lncRNAs that are expressed in the infralimbic prefrontal cortex of adult male mice in response to fear-related learning. Combining these data with cell-type specific ATAC-seq on neurons that had been selectively activated by fear extinction learning, we find inducible 434 lncRNAs that are derived from enhancer regions in the vicinity of protein-coding genes. In particular, we discover an experience-induced lncRNA we call ADRAM (activity-dependent lncRNA associated with memory) that acts as both a scaffold and a combinatorial guide to recruit the brain-enriched chaperone protein 14-3-3 to the promoter of the memory-associated immediate-early gene Nr4a2 and is required fear extinction memory. This study expands the lexicon of experience-dependent lncRNA activity in the brain and highlights enhancer-derived RNAs (eRNAs) as key players in the epigenomic regulation of gene expression associated with the formation of fear extinction memory.
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