Epigenetic mechanisms and consequences of fathering in sticklebacks

 描述(申请人提供)：我们对父亲的理解远远落后于我们对母亲的理解，但父亲对子女的幸福有很大的影响。这个应用程序的总体目标是理解行为、分子和 有助于父亲对后代产生影响的表观遗传机制。核心假设是，父亲和母亲一样，会对后代的行为产生长期的、跨代的影响，这些后果是通过基因组中影响大脑基因表达的表观遗传变化来调节的。这项拟议研究的理论基础是，在一个具有复杂父系行为的易驯服的脊椎动物系统中研究社会行为的自然变异，很可能成功地识别出包括人类在内的其他有机体为父的原因和后果。有两个具体的目标：1：确定父亲对后代的影响的敏感期和分子机制。这一目标的工作假设是，父亲在发育的敏感时期影响后代的基因表达，这会对后代后来的行为产生影响。2：确定父子关系引起的表观遗传改变。这一目标的工作假设是，为人父会导致基因组的表观遗传修饰，从而影响后代大脑基因的表达、行为和压力生理。该项目的预期成果是详细了解不同育儿方式所创造的家庭环境对后代产生保护作用的基本机制。这些结果预计将产生重要的积极影响，因为了解父亲对子女的影响可以促进制定干预措施，促进采用健康的行为。这项拟议中的研究的贡献预计将是详细了解父亲通过一种新的父亲模式系统影响子女的行为、分子和表观遗传机制。这一贡献将是重大的，因为它将揭示父亲是否像母亲一样，可以通过对基因组的表观遗传修改来影响后代。这项拟议的研究具有创新性，因为它利用了一种新的基因组模式生物，在这种模式生物中，父亲是父母照顾的唯一提供者(三刺刺鱼)。使用像刺鱼这样只有父亲照顾的系统的好处是，我们可以将父亲的影响与母亲的影响隔离开来。

 DESCRIPTION (provided by applicant): Our understanding of fathering has lagged far behind our understanding of mothering, yet fathers have a substantial impact on the well-being of their offspring. The overall objective of this application is to understand the behavioral, molecular and epigenetic mechanisms that contribute to the effects of fathering on offspring. The central hypothesis is that fathering, like mothering, has long-lasting, transgenerational consequences for offspring behavior that are mediated via epigenetic changes in the genome that influence brain gene expression. The rationale that underlies the proposed research is that studying natural variation in social behavior in a tractable vertebrate system with sophisticated paternal behaviors is likely to have success identifying the causes and consequences of fathering in other organisms, including humans. There are two specific aims: 1: Identify the sensitive period and the molecular mechanisms underlying the effect of fathering on offspring. The working hypothesis for this aim is that fathering influences offspring gene expression during a sensitive period in development that has consequences for offspring behavior later in life. 2: Identify the epigenetic modifications caused by fathering. The working hypothesis for this aim is that fathering causes epigenetic modifications to the genome that influence offspring brain gene expression, behavior and stress physiology. The expected outcome of this project is a detailed understanding of the basic mechanisms by which family environments created by different fathering styles exert protective effects on offspring. These outcomes are expected to have an important positive impact because understanding the impacts of fathers on offspring could enhance the development of interventions that promote the adoption of healthy behaviors. The contribution of the proposed research is expected to be a detailed understanding of the behavioral, molecular and epigenetic mechanisms by which fathers influence their offspring using a new model system for fathering. This contribution will be significant because it will reveal if fathering, like mothering, can influence subsequent generations via epigenetic modifications to the genome. The proposed research is innovative because it utilizes a new genomically-enabled model organism in which fathers are the sole providers of parental care (threespined stickleback fish). The benefit of using a system with sole paternal care such as sticklebacks is that we can isolate the effects of fathering from the effects of mothering.