The relationship between neurodevelopmental transcriptional programs and insomnia: From Rubinstein-Taybi syndrome into energy metabolism

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Cunha, Lais ; Paschalidis, Mayara ; Moyses-Oliveira, Mariana ; Marquezini, Bruna Pereira ; Deconto, Tais Bassani ; Guerreiro, Pedro ; Kloster, Anna ; Mosini, Amanda Cristina ; Adami, Luana Nayara Gallego ; Andersen, Monica L. ; Tufik, Sergio

• Tipo de documento: Artigo Científico
• Fonte: Sleep Medicine; v. 112, p. 3-pg., 2023-10-05.

Resumo

Neurodevelopmental disorders (NDD) are characterized by cognitive, emotional, and/or motor skills impairment since childhood, and sleep disturbances are a common comorbidity. Rubinstein-Taybi syndrome (RSTS), a rare genetic syndrome associated with NDD, is caused by CREBBP haploinsufficiency. This gene encodes an acetyltransferase with crucial role on the establishment of transcriptional programs during neurodevelopment. Although insomnia has been reported in RSTS patients, the convergent mechanisms between this sleep disturbance and CREBBP loss-of-function are not fully understood. We tested weather the genetic architecture underlying CREBBP regulatory targets and insomnia-associated genes is significantly shared. We then identified the biological pathways enriched among these shared genes. The intersection between CREBBP regulatory targets and genes associated with insomnia included 7 overlapping genes, indicating significantly more overlap than expected by chance. An over-representation analysis on these intersect genes identified pathways related to mitochondrial activity. This finding indicates that the transcriptional programs established by CREBBP might impact insomnia-related biological pathways through the modulation of energy metabolism. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between insomnia and CREBBP regulatory targets. (AU)

• Processo FAPESP: 21/09089-0 - Edição genética em larga escala para o estudo de doenças do neurodesenvolvimento em modelos celulares isogênicos
• Beneficiário: Mariana Moysés Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 20/13467-8 - Relação da apneia obstrutiva do sono e suas comorbidades com a microbiota intestinal: interface com sexualidade e função reprodutiva
• Beneficiário: Monica Levy Andersen
• Modalidade de apoio: Auxílio à Pesquisa - Temático