Department of Developmental Biology and Cancer Research, Hebrew University Medical School, P.O.B. 12272, , Jerusalem, 91120, Israel.
Department of Genetics and Institute for Diabetes Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, 12-126 Translational Research Center, 3400 Civic Center Boulevard Building 421, Philadelphia, PA, 19104-5156, USA.
Nat Commun. 2018 May 23;9(1):2040. doi: 10.1038/s41467-018-04456-6.
Development in mammals is accompanied by specific de novo and demethylation events that are thought to stabilize differentiated cell phenotypes. We demonstrate that a large percentage of the tissue-specific methylation pattern is generated postnatally. Demethylation in the liver is observed in thousands of enhancer-like sequences associated with genes that undergo activation during the first few weeks of life. Using. conditional gene ablation strategy we show that the removal of these methyl groups is stable and necessary for assuring proper hepatocyte gene expression and function through its effect on chromatin accessibility. These postnatal changes in methylation come about through exposure to hormone signaling. These results define the molecular rules of 5-methyl-cytosine regulation as an epigenetic mechanism underlying cellular responses to. changing environment.
哺乳动物的发育伴随着特定的从头和去甲基化事件，这些事件被认为可以稳定分化细胞的表型。我们证明，很大一部分组织特异性甲基化模式是在出生后产生的。在与生命最初几周内激活的基因相关的数千个增强子样序列中观察到肝脏去甲基化。使用条件性基因消融策略，我们表明，去除这些甲基基团是稳定的，并且对于通过影响染色质可及性来确保肝细胞的适当基因表达和功能是必要的。这些甲基化的出生后变化是通过激素信号的暴露产生的。这些结果定义了 5-甲基胞嘧啶调节的分子规则，作为细胞对不断变化的环境的反应的表观遗传机制。
