Genomic Imprinting and the Regulation of Postnatal Neurogenesis.

Anna Lozano-Ureña, Raquel Montalbán-Loro, Anne C Ferguson-Smith, Sacri R Ferrón
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引用次数: 12

Abstract

Most genes required for mammalian development are expressed from both maternally and paternally inherited chromosomal homologues. However, there are a small number of genes known as "imprinted genes" that only express a single allele from one parent, which is repressed on the gene from the other parent. Imprinted genes are dependent on epigenetic mechanisms such as DNA methylation and post-translational modifications of the DNA-associated histone proteins to establish and maintain their parental identity. In the brain, multiple transcripts have been identified which show parental origin-specific expression biases. However, the mechanistic relationship with canonical imprinting is unknown. Recent studies on the postnatal neurogenic niches raise many intriguing questions concerning the role of genomic imprinting and gene dosage during postnatal neurogenesis, including how imprinted genes operate in concert with signalling cues to contribute to newborn neurons' formation during adulthood. Here we have gathered the current knowledge on the imprinting process in the neurogenic niches. We also review the phenotypes associated with genetic mutations at particular imprinted loci in order to consider the impact of imprinted genes in the maintenance and/or differentiation of the neural stem cell pool in vivo and during brain tumour formation.

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基因组印迹与出生后神经发生的调控。
哺乳动物发育所需的大多数基因都是通过母系和父系遗传的染色体同源物来表达的。然而,有少数基因被称为“印迹基因”,它们只表达来自父母一方的单个等位基因,而来自父母另一方的基因则被抑制。印迹基因依赖于表观遗传机制,如DNA甲基化和DNA相关组蛋白的翻译后修饰,以建立和维持其亲本身份。在大脑中,已经确定了多个转录本,这些转录本显示亲本起源特异性表达偏差。然而,与规范印记的机制关系尚不清楚。最近对出生后神经发生龛的研究提出了许多有趣的问题,包括基因组印迹和基因剂量在出生后神经发生中的作用,包括印迹基因如何与信号信号协同作用,促进成年期新生神经元的形成。在这里,我们收集了当前的知识印迹过程在神经源性壁龛。我们还回顾了与特定印迹位点基因突变相关的表型,以考虑印迹基因在体内和脑肿瘤形成过程中对神经干细胞库的维持和/或分化的影响。
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