Center fro Male Reproductive Epigenomics

男性生殖表观基因组学中心

• 批准号: 10260439
• 负责人: Tong Zhou
• 金额: $ 15.93万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-13 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10260439
• 关键词: 3-Dimensional; Age; Alkylation; Animal Model; Animals; Archives; Base Sequence; Bioinformatics; Biological Assay; Cell division; Cells; ChIP-seq; Chemicals; Chromatin; Cytosine; DNA; DNA Methylation; DNA Modification Process; DNA Sequence; Data; Data Set; Databases; Detection; Disease; Enhancers; Environment; Enzymes; Epigenetic Process; Gene Expression; Genes; Genetic Code; Genetic Transcription; Genetic study; Genome; Genotype; Hi-C; High-Throughput Nucleotide Sequencing; Histones; Human; Immunoprecipitation; Individual; Intercistronic Region; Journals; Label; Libraries; Life Style; Link; Location; Mediating; Metabolic; Metabolic Diseases; Methylation; Methyltransferase; Mission; Modification; Mus; Nucleic Acids; Nucleotides; Online Systems; Pattern; Preparation; Process; Proteins; RNA; RNA Sequences; Research Personnel; Ribosomal RNA; Sampling; Series; Services; Sulfhydryl Compounds; Transposase; United States National Institutes of Health; Untranslated RNA; Update; bioinformatics tool; cell type; chromatin modification; computational pipelines; data sharing networks; design; epigenetic regulation; epigenome; epigenomics; genome browser; genome-wide; genomic locus; histone modification; human subject; interest; intergenerational; male; methylation pattern; next generation sequencing; offspring; preservation; promoter; public database; reproductive; single cell analysis; single-cell RNA sequencing; transcriptome sequencing; transcriptomics; transgenerational epigenetic inheritance; translational impact; transmission process; user-friendly; web server; web-accessible

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.

项目概要 传统的遗传学研究是为了研究 DNA 或 RNA 核苷酸信息，而表观遗传学分析的目的是 表征 DNA/RNA 序列和组蛋白内的化学修饰。表观遗传变化 在细胞分裂过程中被保留，并可能修改某些基因的表达，而不是改变 核苷酸序列的遗传密码，这不仅是由于规律和自然发生，而且还受到影响 受多种因素影响，包括年龄、环境/生活方式和疾病状况。更重要的是，一些 表观遗传修饰可能通过跨代表观遗传遗传给后代。 我们最近的研究表明，父系获得的代谢的代际传递 该疾病是由一种称为 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，本次 P50 将重点关注表观遗传特征与 动物模型和人类受试者的代谢紊乱。研究表观遗传调控至关重要 不仅要了解存在哪些类型的修饰，还要了解它们的基因组位点。因此，高通量 测序将用于分析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）将提供必要的、前沿的生物信息专业知识，以促进转化影响 这个高度集成的P50。首先，Core D将协调各个项目的外包文库测序 （具体目标#1）。其次，Core D将提供集中计算服务来存储、处理和 使用我们内部特征明确的管道分析测序数据（具体目标#2）。最后，核心 D 将负责托管一个基于网络的内部服务器来共享组学数据（具体目标#3）， 使内部和外部研究人员可以轻松访问各个项目生成的数据。