A possible role for G-quadruplexes formation and DNA methylation at IMOOD gene promoter in Obsessive Compulsive Disorder

Q1 Biochemistry, Genetics and Molecular Biology Advances in biological regulation Pub Date : 2023-08-01 DOI:10.1016/j.jbior.2023.100976
Annalaura Sabatucci , Antonio Girella , Martina Di Bartolomeo , Mariangela Pucci , Matteo Vismara , Beatrice Benatti , Isobel Alice Blacksell , Dianne Cooper , Enrico Dainese , Fulvio D'Acquisto , Bernardo Dell’Osso , Claudio D'Addario
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Abstract

Obsessive Compulsive Disorder (OCD) is a mental health condition still classified and diagnosed with subjective interview-based assessments and which molecular clues have not completely been elucidated. We have recently identified a new regulator of anxiety and OCD-like behavior called Immuno-moodulin (IMOOD) and, here, we report that IMOOD gene promoter is differentially methylated in OCD subjects when compared to genomic material collected from healthy controls and this alteration is significantly correlated with the increased expression of the gene in OCD. We also demonstrated that IMOOD promoter can form G-quadruplexes and we suggest that, in homeostatic conditions, these structures could evoke DNA-methylation silencing the gene, whereas in pathological conditions, like OCD, could induce gene expression making the promoter more accessible to transcriptional factors. We here thus further suggest IMOOD as a new biomarker for OCD and also hypothesize new mechanisms of gene regulation.

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G四链体形成和IMOOD基因启动子DNA甲基化在强迫症中的可能作用。
强迫症(OCD)是一种心理健康状况,仍通过基于主观访谈的评估进行分类和诊断,其分子线索尚未完全阐明。我们最近发现了一种新的焦虑和强迫症样行为的调节因子,称为Immuno-moodulin(IMOOD)。在这里,我们报道了与从健康对照组收集的基因组材料相比,强迫症受试者的IMOOD基因启动子被不同地甲基化,这种改变与该基因在强迫症中的表达增加显著相关。我们还证明了IMOOD启动子可以形成G-四链体,我们认为,在稳态条件下,这些结构可以引起DNA甲基化沉默基因,而在病理条件下,如强迫症,可以诱导基因表达,使启动子更容易被转录因子接近。因此,我们在这里进一步建议IMOOD作为强迫症的一种新的生物标志物,并假设了基因调控的新机制。
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来源期刊
Advances in biological regulation
Advances in biological regulation Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
8.90
自引率
0.00%
发文量
41
审稿时长
17 days
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