Reizel Yitzhak, Spiro Adam, Sabag Ofra, Skversky Yael, Hecht Merav, Keshet Ilana, Berman Benjamin P, Cedar Howard
Department of Developmental Biology and Cancer Research, Hebrew University Medical School, Jerusalem 91120, Israel;
Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel;
Genes Dev. 2015 May 1;29(9):923-33. doi: 10.1101/gad.259309.115.
DNA methylation patterns are set up in a relatively fixed programmed manner during normal embryonic development and are then stably maintained. Using genome-wide analysis, we discovered a postnatal pathway involving gender-specific demethylation that occurs exclusively in the male liver. This demodification is programmed to take place at tissue-specific enhancer sequences, and our data show that the methylation state at these loci is associated with and appears to play a role in the transcriptional regulation of nearby genes. This process is mediated by the secretion of testosterone at the time of sexual maturity, but the resulting methylation profile is stable and therefore can serve as an epigenetic memory even in the absence of this inducer. These findings add a new dimension to our understanding of the role of DNA methylation in vivo and provide the foundations for deciphering how environment can impact on the epigenetic regulation of genes in general.
在正常胚胎发育过程中，DNA甲基化模式以相对固定的程序化方式建立，然后稳定维持。通过全基因组分析，我们发现了一条出生后途径，涉及仅在雄性肝脏中发生的性别特异性去甲基化。这种去修饰被编程在组织特异性增强子序列处发生，我们的数据表明这些位点的甲基化状态与附近基因的转录调控相关，并且似乎在其中发挥作用。这个过程由性成熟时睾酮的分泌介导，但由此产生的甲基化图谱是稳定的，因此即使在没有这种诱导物的情况下也可以作为一种表观遗传记忆。这些发现为我们理解DNA甲基化在体内的作用增添了新的维度，并为破译环境如何总体上影响基因的表观遗传调控提供了基础。
