Diet, Epigenetic Events, And Cancer Prevention

饮食、表观遗传事件和癌症预防

基本信息

批准号：
6958770
负责人：
David Ian Kingston Martin
金额：
$ 31.62万
依托单位：
CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-01 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6958770
关键词：
CpG islands alleles cancer prevention cancer risk cytosine dietary supplements gene induction /repression laboratory mouse methylation nucleic acid sequence nutrition aspect of cancer nutrition related tag obesity phenotype

项目摘要

DESCRIPTION (provided by applicant): In cancer, normal epigenetic silencing and cytosine methylation are disrupted. Dietary intake of methyl donors can directly affect epigenetic mechanisms through cytosine methylation. Our longterm goal is to understand how the risk of human disease, cancer in particular, is affected by epigenetics and diet. We use A10-vy (obese yellow) mice, a model that exhibits a highly variable phenotype of obesity, tumors, and type II diabetes; the expression of the syndrome is under epigenetic control. The epigenetic state of the A-vy allele can be inherited, indicating that the epigenetic marks determining the behavior of the allele are maintained in the germline. Supplementation of the maternal A-vy diet with methyl donors during gestation alters phenotypes in offspring. We hypothesize that continuous supplementation of the maternal diet with methyl donors will produce a cumulative increase in methylation of the A-vy allele, resulting in a multigenerational trend toward suppression of the obese yellow phenotype, and denser methylation of the allele. The changes may persist after supplementation is withdrawn. Our specific aims are: 1. Investigate the effects of continuous methyl donor supplementation on inheritance of the obese yellow phenotype in A-vy mice. Continuous feeding of methyl donors to A-vy mothers may produce changes in phenotype that increase with more generations. 2. Ask if the effects of methyl donor supplementation persist for generations when supplementation is withdrawn. Changes induced by methyl donors may be maintained in the germline, resulting in epigenetic "memory" that persists for one or more generations. 3. Investigate effects of methyl donor supplementation on CpG methylation of the A-vy allele We will use bisulphite allelic sequencing to obtain a detailed picture of the methylation status of the allele in mice bred for Aims 1 and 2.

描述（由申请人提供）：在癌症中，正常的表观遗传沉默和胞嘧啶甲基化被破坏。甲基供体的饮食摄入可以直接通过胞嘧啶甲基化影响表观遗传机制。我们的长期目标是了解表观遗传学和饮食的影响，尤其是癌症的风险如何。我们使用A10-VY（肥胖黄色）小鼠，该模型表现出高度可变的肥胖，肿瘤和II型糖尿病的表型。该综合征的表达在表观遗传控制之下。 A-VY等位基因的表观遗传状态可以遗传，表明确定等位基因行为的表观遗传标记保持在种系中。在妊娠期间，用甲基供体补充母体A-VY饮食会改变后代的表型。我们假设，用甲基供体连续补充母体饮食将产生A-VY等位基因的甲基化累积增加，从而导致抑制肥胖黄色表型的多代趋势，并使等位基因的甲基化密集。补充后可能会持续进行更改。我们的具体目的是：1。研究补充甲基供体对A-VY小鼠肥胖黄色表型的遗传的影响。将甲基供体连续喂养向A-Vy母亲可能会导致表型的变化，而随着世代的增加而增加。 2.询问补充补充剂时，补充甲基供体的影响是否持续存在。甲基供体引起的变化可以保持在种系中，从而导致表观遗传“记忆”持续了一个或多代。 3.研究补充甲基供体对A-VY等位基因的CpG甲基化的影响，我们将使用Bisulphite等位基因测序来获得育种的小鼠甲基化状态的详细图片，以繁殖为AIM 1和2。