权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Regulatory elements of replication timing and 3D genome organization

复制时间和 3D 基因组组织的调控元件

基本信息

批准号：
10808426
负责人：
Juan Carlos Rivera-Mulia
金额：
$ 1.01万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

项目摘要

PROJECT SUMMARY Increasing evidence indicates that 3D genome architecture is required to regulate gene function and its alterations are associated with many diseases. The genome is organized into compartments that align with the temporal order of DNA replication (replication timing – RT). However, little is known about the mechanisms underlying RT control and 3D genome organization. Recently, we identified a novel class of cis regulatory elements that control RT and 3D genome organization: early replicating control elements – ERCEs. Our long-term goals are to study what are the regulatory elements of genome organization in human differentiated cell types, investigate how trans-acting factors control these elements, and define how 3D genome organization is remodeled during development and evolution. To achieve these goals, we are deleting and inserting candidate ERCEs into the genome of human differentiated cell types and testing their effects on RT, 3D genome organization and gene expression. We are also exploiting highly synchronous human embryonic stem cells differentiation systems to track ERCE activation during cell fate commitment. Finally, to better understand how the genome was remodeled during evolution, we are performing comparative analyses of 3D genome organization and function using primary cells derived from different species. Overall, we expect that our work will contribute significantly to understand the fundamental principles of genome organization and its relationship to gene function.

项目摘要越来越多的证据表明，3D基因组结构是调节基因功能所必需的，改变与许多疾病有关。基因组被组织成间隔排列与DNA复制的时间顺序（复制时间- RT）。然而，人们对此知之甚少。 RT控制和3D基因组组织的潜在机制。最近，我们发现了一个新的类，控制RT和3D基因组组织的顺式调控元件：早期复制控制元素-ERCE。我们的长期目标是研究基因组的调节元件是什么组织在人类分化的细胞类型，调查如何反式作用因子控制这些元素，并定义了3D基因组组织在发育和进化过程中如何重塑。到为了实现这些目标，我们正在删除和插入候选ERCE到人类基因组中，分化的细胞类型，并测试它们对RT、3D基因组组织和基因表达的影响。我们还利用高度同步的人类胚胎干细胞分化系统来跟踪 ERCE在细胞命运定型过程中的激活。最后，为了更好地理解基因组是如何在进化过程中重塑，我们正在进行3D基因组组织的比较分析，使用来自不同物种的原代细胞发挥功能。总体而言，我们预计我们的工作将有助于理解基因组组织的基本原理及其与基因功能的关系

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

You shall not pass! Unveiling the barriers for cohesin-mediated loop extrusion.

DOI：
10.1016/j.molcel.2022.06.028
发表时间：
2022-07-21
期刊：
MOLECULAR CELL
影响因子：
16
作者：
Meyer-Nava, Silvia;Rivera-Mulia, Juan Carlos
通讯作者：
Rivera-Mulia, Juan Carlos

Optimized Repli-seq: improved DNA replication timing analysis by next-generation sequencing.

DOI：
10.1007/s10577-022-09703-7
发表时间：
2022-12
期刊：
CHROMOSOME RESEARCH
影响因子：
2.6
作者：
Rivera-Mulia, Juan Carlos;Trevilla-Garcia, Claudia;Martinez-Cifuentes, Santiago
通讯作者：
Martinez-Cifuentes, Santiago

Epigenomic signatures associated with spontaneous and replication stress-induced DNA double strand breaks.