Traduction partielle: G.M.
Autism Res Treat. 2013;2013:826156. Epub 2013 Sep 15.
Epigénétique et autisme
Source
Department of Physiology & Biophysics, The Howard University College of Medicine, Washington, DC 20059, USA.Abstract
Cet
compte-rendu identifie les mécanismes pour modifier les interactions ADN -
histones altérées de la chromatine cellulaire pour réguler positivement ou
réguler négativement l'expression des gènes qui pourraient servir de
cibles épigénétiques pour des interventions thérapeutiques dans
l'autisme .
DNA methyltransferases (DNMTs) can phosphorylate histone H3 at T6. Aided by protein kinase C β 1, the DNMT lysine-specific demethylase-1 prevents demethylation of H3 at K4. During androgen-receptor-(AR-) dependent gene activation, this sequence may produce AR-dependent gene overactivation which may partly explain the male predominance of autism. AR-dependent gene overactivation in conjunction with a DNMT mechanism for methylating oxytocin receptors could produce high arousal inputs to the amygdala resulting in aberrant socialization, a prime characteristic of autism. Dysregulation of histone methyltransferases and histone deacetylases (HDACs) associated with low activity of methyl CpG binding protein-2 at cytosine-guanine sites in genes may reduce the capacity for condensing chromatin and silencing genes in frontal cortex, a site characterized by decreased cortical interconnectivity in autistic subjects. HDAC1 inhibition can overactivate mRNA transcription, a putative mechanism for the increased number of cerebral cortical columns and local frontal cortex hyperactivity in autistic individuals.
Ces mécanismes épigénétiques sous -jacents de la prédominance masculine, l'interaction sociale aberrante, et faible fonctionnement du cortex frontal peuvent-être de nouvelles cibles pour les stratégies de traitement et de prévention de l'autisme.
DNA methyltransferases (DNMTs) can phosphorylate histone H3 at T6. Aided by protein kinase C β 1, the DNMT lysine-specific demethylase-1 prevents demethylation of H3 at K4. During androgen-receptor-(AR-) dependent gene activation, this sequence may produce AR-dependent gene overactivation which may partly explain the male predominance of autism. AR-dependent gene overactivation in conjunction with a DNMT mechanism for methylating oxytocin receptors could produce high arousal inputs to the amygdala resulting in aberrant socialization, a prime characteristic of autism. Dysregulation of histone methyltransferases and histone deacetylases (HDACs) associated with low activity of methyl CpG binding protein-2 at cytosine-guanine sites in genes may reduce the capacity for condensing chromatin and silencing genes in frontal cortex, a site characterized by decreased cortical interconnectivity in autistic subjects. HDAC1 inhibition can overactivate mRNA transcription, a putative mechanism for the increased number of cerebral cortical columns and local frontal cortex hyperactivity in autistic individuals.
Ces mécanismes épigénétiques sous -jacents de la prédominance masculine, l'interaction sociale aberrante, et faible fonctionnement du cortex frontal peuvent-être de nouvelles cibles pour les stratégies de traitement et de prévention de l'autisme.
- PMID: 24151554
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