Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Department of Pediatrics, Yong-He Cardinal Tien Hospital, Taipei 234, Taiwan.
Hum Mol Genet. 2018 Mar 15;27(6):1039-1054. doi: 10.1093/hmg/ddy023.
Visual system development is light-experience dependent, which strongly implicates epigenetic mechanisms in light-regulated maturation. Among many epigenetic processes, genomic imprinting is an epigenetic mechanism through which monoallelic gene expression occurs in a parent-of-origin-specific manner. It is unknown if genomic imprinting contributes to visual system development. We profiled the transcriptome and imprintome during critical periods of mouse visual system development under normal- and dark-rearing conditions using B6/CAST F1 hybrid mice. We identified experience-regulated, isoform-specific and brain-region-specific imprinted genes. We also found imprinted microRNAs were predominantly clustered into the Dlk1-Dio3 imprinted locus with light experience affecting some imprinted miRNA expression. Our findings provide the first comprehensive analysis of light-experience regulation of the transcriptome and imprintome during critical periods of visual system development. Our results may contribute to therapeutic strategies for visual impairments and circadian rhythm disorders resulting from a dysfunctional imprintome.
视觉系统的发育依赖于光体验，这强烈暗示了表观遗传机制在光调节成熟中的作用。在众多表观遗传过程中，基因组印记是一种表观遗传机制，通过这种机制，单等位基因以亲本来源特异性的方式表达。目前尚不清楚基因组印记是否有助于视觉系统的发育。我们使用 B6/CAST F1 杂交小鼠，在正常和黑暗饲养条件下，对视觉系统发育关键期的转录组和印记组进行了分析。我们鉴定出了受体验调节的、异构体特异性的和脑区特异性的印记基因。我们还发现，印记 microRNAs 主要聚类到 Dlk1-Dio3 印记基因座，光体验影响一些印记 microRNA 的表达。我们的研究结果提供了视觉系统发育关键期转录组和印记组受光体验调节的首次全面分析。我们的研究结果可能为治疗因印记组功能障碍导致的视觉障碍和昼夜节律紊乱提供策略。
