| First Author | Rusconi F | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 13 | Pages | 3651-6 |
| PubMed ID | 26976584 | Mgi Jnum | J:232045 |
| Mgi Id | MGI:5775845 | Doi | 10.1073/pnas.1511974113 |
| Citation | Rusconi F, et al. (2016) LSD1 modulates stress-evoked transcription of immediate early genes and emotional behavior. Proc Natl Acad Sci U S A 113(13):3651-6 |
| abstractText | Behavioral changes in response to stressful stimuli can be controlled via adaptive epigenetic changes in neuronal gene expression. Here we 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, we 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) andc-fos Deletion or reduction of neuroLSD1 in mutant mice translates into decreased levels of activating histone marks ategr1andc-fospromoters, dampening their psychosocial stress-induced transcription and resulting in low anxiety-like behavior. Administration of suberoylanilide hydroxamine to neuroLSD1(KO)mice reactivatesegr1andc-fostranscription 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. |
