Center fro Male Reproductive Epigenomics

项目摘要 虽然传统的遗传学研究是研究DNA或RNA核苷酸信息，但表观遗传学分析的目标是 描述DNA/RNA序列和组蛋白蛋白中的化学修饰。表观遗传变化 在细胞分裂过程中被保存，并可能改变某些基因的表达，而不是改变 核苷酸序列的遗传密码，这不仅是由于定期和自然发生的，而且还受到影响 由年龄、环境/生活方式和疾病状况等几个因素决定。更重要的是，有些人 表观遗传修饰可能通过跨代表观遗传传递给后代。 我们最近的研究表明，父系获得性代谢的这种代际传递 疾病是由一种名为DNA(胞嘧啶-5-)-甲基转移酶2的核酸修饰酶介导的 (DNMT2)。受这些发现的启发，这篇P50将关注表观遗传学特征和 动物模型和人类受试者的代谢紊乱。研究表观遗传调控是至关重要的。 不仅要知道存在哪些类型的修饰，而且要知道它们的基因组位置。因此，高吞吐量 测序将被应用于描述动物和人类样本的表观遗传变化。这个表观基因组学 核心(核心D)将提供基本的、尖端的生物信息专业知识，以促进翻译影响 这个高度集成的P50。首先，核心D将协调各个项目的外包库排序 (具体目标1)。其次，Core D将提供集中计算服务来存储、处理和 使用我们内部特征良好的管道分析测序数据(具体目标2)。最后，核心 D将负责托管内部基于网络的服务器，以共享组学数据(具体目标3)，这 为内部和外部研究人员提供对单个项目生成的数据的轻松访问。

Project Summary While traditional genetic studies to investigate DNA or RNA nucleotide information, epigenetic analyses aim to characterize chemical modifications within both DNA/RNA sequences and histone proteins. Epigenetic changes are preserved during cell division and potentially modify the expression of certain genes instead of altering the genetic code of nucleotide sequences, which is not only due to regular and natural occurrence but also influenced by several factors including age, the environment/lifestyle, and disease status. More importantly, some epigenetic modifications can potentially be transmitted to offspring by transgenerational epigenetic inheritance. Our more recent study suggests that this intergenerational transmission of paternally acquired metabolic disorders is mediated by a nucleic acid modification enzyme called DNA (cytosine-5-)-methyltransferase 2 (Dnmt2). Inspired by these findings, this P50 will focus on the relationship between epigenetic profiles and metabolic disorders in both animal models and human subjects. To study the epigenetic regulation, it is critical to know not only what kinds of modifications are present but also their genomic loci. Therefore, high-throughput sequencing will be applied to profile epigenetic alterations in both animal and human samples. This Epigenomics Core (Core D) will provide essential, cutting edge, bioinformatical expertise to facilitate the translational impact of this highly integrated P50. Firstly, Core D will coordinate outsource library sequencing for individual projects (Specific Aim #1). Secondly, Core D will provide centralized computational service to store, process, and analyze the sequencing data, using our in-house well-characterized pipelines (Specific Aims #2). Finally, Core D will be responsible for hosting an in-house web-based server to share the omics data (Specific Aim #3), which provides both the internal and external researchers an easy access to the data generated from individual projects.