Perez Julio D, Rubinstein Nimrod D, Dulac Catherine
Department of Molecular and Cellular Biology, Harvard University, Howard Hughes Medical Institute, Cambridge, Massachusetts 02138; email:
Annu Rev Neurosci. 2016 Jul 8;39:347-84. doi: 10.1146/annurev-neuro-061010-113708. Epub 2016 Apr 25.
Mammalian evolution entailed multiple innovations in gene regulation, including the emergence of genomic imprinting, an epigenetic regulation leading to the preferential expression of a gene from its maternal or paternal allele. Genomic imprinting is highly prevalent in the brain, yet, until recently, its central roles in neural processes have not been fully appreciated. Here, we provide a comprehensive survey of adult and developmental brain functions influenced by imprinted genes, from neural development and wiring to synaptic function and plasticity, energy balance, social behaviors, emotions, and cognition. We further review the widespread identification of parental biases alongside monoallelic expression in brain tissues, discuss their potential roles in dosage regulation of key neural pathways, and suggest possible mechanisms underlying the dynamic regulation of imprinting in the brain. This review should help provide a better understanding of the significance of genomic imprinting in the normal and pathological brain of mammals including humans.
哺乳动物的进化在基因调控方面带来了多项创新,包括基因组印记的出现,这是一种表观遗传调控,导致基因从其母本或父本等位基因中优先表达。基因组印记在大脑中高度普遍,然而,直到最近,其在神经过程中的核心作用尚未得到充分认识。在这里,我们全面综述了受印记基因影响的成年和发育大脑功能,从神经发育和神经连接到突触功能和可塑性、能量平衡、社会行为、情绪和认知。我们进一步回顾了在脑组织中与单等位基因表达同时广泛存在的亲本偏向性的鉴定,讨论了它们在关键神经通路剂量调节中的潜在作用,并提出了大脑中印迹动态调控的可能机制。这篇综述应有助于更好地理解基因组印记在包括人类在内的哺乳动物正常和病理大脑中的重要性。