Core 3: Epigenomics Core

核心 3：表观基因组学核心

• 批准号: 9788056
• 负责人: Charles B Epstein
• 金额: $ 30.86万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9788056
• 关键词: Adopted; Algorithms; Cell Count; Cells; ChIP-seq; Chromatin; Chromatin Structure; Clinical; Clinical Trials; Data; Diagnosis; Enrollment; Epigenetic Process; Gene Expression; Gene Expression Regulation; Genetic Enhancer Element; Genomics; Goals; Maps; Mission; Molecular; Multiple Myeloma; Patients; Procedures; Relapse; Sampling; Standardization; Therapeutic; Time; Variant; base; cancer genomics; cofactor; epigenomics; histone modification; improved; innovation; neoplastic cell; new therapeutic target; pre-clinical; programs; transcription factor

Project Summary (Core 3) The overall goal of the program is to study the key features of epigenetic circuitry in myeloma and improve our understanding of global gene regulation to deploy novel therapeutics that target key epigenomic circuits. Cells and cell states can be defined by their gene expression programs, and tumor cells commonly have deregulated gene expression programs. This core will perform epigenomic analyses on clinical samples from Projects 1, 2, and 4, as well as preclinical samples in Project 2 and 3. Specifically, samples will be obtained from patients enrolled on the clinical trial (N=1260) evaluating an MRD-based therapeutic algorithm at time of diagnosis (Project 1 and 2) and at relapse (Project 4). In each case, tumor cells will be isolated in Core 2 using well established procedures. This core (Core 3) will perform analysis for select master transcription factors, their chromatin cofactors, and the enhancer element marks. The core has capabilities to perform ChIP-seq using low cell number (5000 cells; van Galen et al, Molecular Cell 2016 Jan;61(1):1-11), perform Single-cell ChIP- seq (Rotem A et al Nat Biotechnol. 2015 Nov;33(11):1165-72) as well as adopt innovative variations specifically needed to answer questions. The core will help accurately chart maps of histone modifications and related chromatin structures.

项目摘要（核心 3） 该计划的总体目标是研究骨髓瘤表观遗传回路的关键特征并提高我们的研究水平。 了解全球基因调控，以部署针对关键表观基因组回路的新型疗法。细胞 细胞状态可以通过它们的基因表达程序来定义，肿瘤细胞通常已经失调 基因表达程序。该核心将对项目 1、2、 和4，以及项目2和3中的临床前样本。具体来说，样本将从患者身上获得 参加临床试验 (N=1260)，评估诊断时基于 MRD 的治疗算法 （项目 1 和 2）和复发时（项目 4）。在每种情况下，肿瘤细胞都将在 Core 2 中使用孔进行分离 既定程序。该核心（核心 3）将对选定的主转录因子、它们的 染色质辅助因子和增强子元件标记。该核心具有执行 ChIP-seq 的能力 低细胞数（5000 个细胞；van Galen 等人，Molecular Cell 2016 Jan；61(1):1-11），执行单细胞 ChIP- seq (Rotem A et al Nat Biotechnol. 2015 Nov;33(11):1165-72) 以及采用创新变异 特别需要回答问题。该核心将有助于准确绘制组蛋白修饰图谱 相关的染色质结构。