Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
J Mol Endocrinol. 2011 Sep 19;47(2):R67-74. doi: 10.1530/JME-11-0065. Print 2011 Oct.
Genomic imprinting is an important and enigmatic form of gene regulation in mammals in which one copy of a gene is silenced in a manner determined by its parental history. Imprinted genes range from those with constitutive monoallelic silencing to those, typically more remote from imprinting control regions, that display developmentally regulated, tissue-specific or partial monoallelic expression. This diversity may make these genes, and the processes they control, more or less sensitive to factors that modify or disrupt epigenetic marks. Imprinted genes have important functions in development and physiology, including major endocrine/neuroendocrine axes. Owing to is central role in coordinating growth, metabolism and reproduction, as well as evidence from genetic and knockout studies, the hypothalamus may be a focus for imprinted gene action. Are there unifying principles that explain why a gene should be imprinted? Conflict between parental genomes over limiting maternal resources, but also co-adaptation between mothers and offspring, have been invoked to explain the evolution of imprinting. Recent reports suggest there may be many more genes imprinted in the hypothalamus than hitherto expected, and it will be important for these new candidates to be validated and to determine whether they conform to current notions of how imprinting is regulated. In fully evaluating the role of imprinted genes in the hypothalamus, much work needs to be done to identify the specific neuronal populations in which particular genes are expressed, establish whether there are pathways in common and whether imprinted genes are involved in long-term programming of hypothalamic functions.
基因组印迹是哺乳动物中一种重要而神秘的基因调控形式，其中一个基因的一个拷贝以其亲本历史决定的方式沉默。印迹基因的范围从那些具有组成型单等位基因沉默的基因到那些通常离印迹控制区域更远的基因，它们表现出发育调控、组织特异性或部分单等位基因表达。这种多样性可能使这些基因及其控制的过程或多或少对改变或破坏表观遗传标记的因素敏感。印迹基因在发育和生理过程中具有重要功能，包括主要的内分泌/神经内分泌轴。由于其在协调生长、代谢和生殖中的核心作用，以及遗传和敲除研究的证据，下丘脑可能是印迹基因作用的焦点。是否有统一的原则可以解释为什么一个基因应该被印迹？父母基因组之间对有限母本资源的竞争，以及母亲和后代之间的共同适应，被用来解释印迹的进化。最近的报告表明，在下丘脑可能有比预期更多的基因被印迹，对于这些新的候选基因，重要的是要对其进行验证，并确定它们是否符合当前对印迹调控的认识。在充分评估印迹基因在下丘脑的作用时，需要做大量工作来确定特定基因在特定神经元群体中的表达，确定是否存在共同途径，以及印迹基因是否参与下丘脑功能的长期编程。
