Ojeda Sergio R, Lomniczi Alejandro, Sandau Ursula, Matagne Valerie
Endocr Dev. 2010;17:44-51. doi: 10.1159/000262527. Epub 2009 Nov 24.
The initiation of mammalian puberty requires an increased pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This increase is brought about by changes in transsynaptic and glial-neuronal communication. Coordination of these cellular interactions likely requires the participation of sets of genes hierarchically arranged within functionally connected networks. Using high throughput, genetic, molecular and bioinformatics strategies, in combination with a systems biology approach, three transcriptional regulators of the pubertal process have been identified, and the structure of at least one hypothalamic gene network has been proposed. A genomewide analysis of hypothalamic DNA methylation revealed profound changes in methylation patterns associated with the onset of female puberty. Pharmacological disruption of two epigenetic marks associated with gene silencing (DNA methylation and histone deacetylation) resulted in pubertal failure, instead of advancing the onset of puberty, suggesting that disruption of these two silencing mechanisms leads to activation of repressor genes whose expression would normally decrease at puberty. These observations suggest that the genetic underpinnings of puberty are polygenic rather than specified by a single gene, and that epigenetic mechanisms may provide coordination and transcriptional plasticity to this genetic network.
哺乳动物青春期的启动需要下丘脑促性腺激素释放激素（GnRH）脉冲式释放增加。这种增加是由跨突触和神经胶质-神经元通讯的变化引起的。这些细胞间相互作用的协调可能需要在功能连接网络中分层排列的基因集的参与。运用高通量、遗传学、分子和生物信息学策略，并结合系统生物学方法，已鉴定出青春期过程的三种转录调节因子，并提出了至少一个下丘脑基因网络的结构。对下丘脑DNA甲基化的全基因组分析揭示了与女性青春期开始相关的甲基化模式的深刻变化。对与基因沉默相关的两种表观遗传标记（DNA甲基化和组蛋白去乙酰化）进行药理学破坏导致青春期发育失败，而不是提前青春期开始，这表明破坏这两种沉默机制会导致阻遏基因激活，而这些基因的表达在青春期通常会降低。这些观察结果表明，青春期的遗传基础是多基因的，而非由单个基因决定，并且表观遗传机制可能为该基因网络提供协调性和转录可塑性。
