酵母和人类细胞中表观遗传过程的营养控制。
Nutritional control of epigenetic processes in yeast and human cells.
机构信息
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3220.
出版信息
Genetics. 2013 Nov;195(3):831-44. doi: 10.1534/genetics.113.153981. Epub 2013 Aug 26.
Abstract
The vitamin folate is required for methionine homeostasis in all organisms. In addition to its role in protein synthesis, methionine is the precursor to S-adenosyl-methionine (SAM), which is used in myriad cellular methylation reactions, including all histone methylation reactions. Here, we demonstrate that folate and methionine deficiency led to reduced methylation of lysine 4 of histone H3 (H3K4) in Saccharomyces cerevisiae. The effect of nutritional deficiency on H3K79 methylation was less pronounced, but was exacerbated in S. cerevisiae carrying a hypomorphic allele of Dot1, the enzyme responsible for H3K79 methylation. This result suggested a hierarchy of epigenetic modifications in terms of their susceptibility to nutritional limitations. Folate deficiency caused changes in gene transcription that mirrored the effect of complete loss of H3K4 methylation. Histone methylation was also found to respond to nutritional deficiency in the fission yeast Schizosaccharomyces pombe and in human cells in culture.
摘要
维生素叶酸是所有生物中甲硫氨酸稳态所必需的。除了在蛋白质合成中的作用外，甲硫氨酸还是 S-腺苷甲硫氨酸（SAM）的前体，SAM 用于无数细胞甲基化反应，包括所有组蛋白甲基化反应。在这里，我们证明了叶酸和甲硫氨酸缺乏会导致酿酒酵母中组蛋白 H3 赖氨酸 4（H3K4）的甲基化减少。营养缺乏对 H3K79 甲基化的影响不那么明显，但在携带 Dot1 （负责 H3K79 甲基化的酶）功能减弱等位基因的酿酒酵母中则更为严重。这一结果表明，表观遗传修饰的层次与其对营养限制的敏感性有关。叶酸缺乏导致基因转录发生变化，这与完全丧失 H3K4 甲基化的效果相似。在裂殖酵母 Schizosaccharomyces pombe 和培养的人类细胞中也发现组蛋白甲基化对营养缺乏有反应。
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