The SWI/SNF complex sub-unit Bap60 is required for training-induced gene transcription during long-term memory formation
Notice bibliographique
Résumé
Abstract Long-term memory (LTM) formation requires tightly regulated gene expression in response to neuronal activity. Chromatin remodeling is thought to play a role in enabling this transcriptional response, but the specific mechanisms remain unclear. In Drosophila , a transcriptional trace of courtship LTM training can be observed in the mushroom body (MB) during the memory consolidation phase after the end of training. Here, we investigated the role of Bap60, a core subunit of the Drosophila SWI/SNF chromatin remodeling complex, in the transcriptional trace of memory consolidation. Adult-specific knockdown of Bap60 in the MB selectively impaired LTM with short-term memory (STM) left intact. Transcriptome analysis of Bap60 knockdown MBs following courtship LTM training revealed near complete disruption of LTM training induced transcription in the MB. MB-specific CUT&RUN was used to map SWI/SNF binding sites and identify over 100 candidate direct Bap60-dependent training induced genes. Bap60 was not required for training induced activation of immediate early genes (IEGs), Hr38 and Sr, which are transcription factors that are critical for courtship LTM. This suggests that Bap60 may regulate LTM gene induction downstream of IEGs. Interestingly, we identified Sr binding sites at 30% of Bap60-dependent training induced genes. Many of these target genes were transcription factors, including Prospero (Pros), which we show is also required in the MB for LTM but not STM. Interestingly, Pros is induced in a subset of MB nuclei, suggesting Bap60 is involved in cell specific LTM training induced gene activation. Together, these findings reveal a critical role for Bap60, a core SWI/SNF subunit, as a key regulator of LTM training-induced transcription downstream of IEGs. Significance Statement Autosomal dominant mutations in SWI/SNF subunits are a leading cause of neurodevelopmental disorders (NDDs) including Autism and Intellectual Disability. Therefore, understanding their role in brain function can provide insight into the mechanisms underlying human disease. The SWI/SNF complex is an important chromatin remodeling complex that is conserved from yeast to mammals. This large protein complex is a transcriptional coactivator that uses energy from ATP to open up chromatin and create binding sites for transcription factors. Our knowledge about how SWI/SNF functions in different cell types of the brain is highly limited. In this study we investigate the Bap60 component of SWI/SNF in memory neurons of the fruit fly, Drosophila melanogaster . We find that Bap60 is required for activation of gene expression programs underlying long term memory consolidation. Dynamic gene expression, like that associated with LTM, is essential to build neural circuits during human cognitive development. It is therefore possible that this process is disrupted in people with SWI/SNF-related NDDs.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».