Regulation of chromatin folding in space and time
染色质折叠在空间和时间上的调节
基本信息
- 批准号:10429968
- 负责人:
- 金额:$ 40.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-07-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AneuploidyAnimal ModelBiological AssayCell NucleusCellsChromatinChromatin LoopChromosome PositioningChromosomesComplexDNADevelopmentDiseaseEnhancersFluorescent in Situ HybridizationGenesGenetic TranscriptionGenomeGenomicsGoalsHumanIn SituInheritedLeadMalignant NeoplasmsMethodsMitotic RecombinationMolecularNuclearPositioning AttributePreventionPublic HealthRegulationResolutionTechnologyTimeTranslatingWorkbasegene functiongenetic informationnew therapeutic targetnovelthree dimensional structuretool
项目摘要
Abstract
Eukaryotic genomes encode genetic information in their linear sequence, but appropriate expression of
their genes requires chromosomes to fold into complex and spatially distinct three-dimensional structures.
Recent advances in genomic-based approaches have uncovered a hierarchy of DNA interactions, from small
chromatin loops that connect genes and enhancers to larger chromosomal domains and nuclear
compartments. However, despite the remarkable conservation of these organizational features and their
impact on gene function, we have a very limited understanding of how chromosomes are spatially partitioned,
functionally packaged, and relatively positioned in the nucleus. Technical limitations have also hindered our
ability to ask questions regarding cell-to-cell variability and the relationship between chromatin folding,
positioning, and function at single cell resolution.
Our previous studies involved the development of two technologies that use fluorescent in situ
hybridization (FISH) to interrogate chromosome positioning at single-cell resolution. Our goal is to build on this
work and use these tools to elucidate how chromosomal segments find each other and then form stable
interactions within cells. I can envision three immediate stages for our work. The first is developing a rapid and
precise method for identifying candidates involved in chromosome interactions. The second is establishing a
battery of in situ-based assays that can be used to characterize the candidates, and the third is translating our
findings from model organisms to humans. Collectively, the studies proposed here will uncover novel molecular
mechanisms underlying nuclear organization, providing a new avenue to study how chromatin folding and
positioning is established and inherited, and how dysfunctional organization contributes to disease.
摘要
真核基因组以其线性序列编码遗传信息,但适当地表达
他们的基因需要染色体折叠成复杂的、空间上不同的三维结构。
基因组方法的最新进展揭示了DNA相互作用的层次结构,从小到小
将基因和增强子连接到更大的染色体区域和核的染色质环
车厢。然而,尽管这些组织特征和它们的
对基因功能的影响,我们对染色体是如何在空间上分割的了解非常有限,
功能包装,并相对定位在细胞核内。技术限制也阻碍了我们的
能够提出关于细胞间的可变性和染色质折叠之间的关系的问题,
定位,并在单个单元分辨率下工作。
我们之前的研究包括开发两种使用原位荧光的技术
杂交(FISH)在单细胞分辨率下询问染色体定位。我们的目标是在此基础上再接再厉
研究并使用这些工具来阐明染色体片段是如何找到彼此并形成稳定的
细胞内的相互作用。我可以设想我们的工作立即进入三个阶段。首先是开发一种快速和
精确识别参与染色体相互作用的候选者的方法。第二个是建立一个
一组基于现场的分析,可以用来表征候选人的特征,第三个是翻译我们的
从模型生物到人类的发现。总的来说,这里提出的研究将揭示新的分子
核组织的潜在机制,为研究染色质折叠和
定位是建立和遗传的,以及组织功能失调如何导致疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Eric F. Joyce其他文献
B cell stimulation changes the structure and higher-order organization of the inactive X chromosome
B 细胞刺激改变了非活性 X 染色体的结构和高阶组织。
- DOI:
10.1016/j.celrep.2025.115351 - 发表时间:
2025-03-25 - 期刊:
- 影响因子:6.900
- 作者:
Isabel Sierra;Natalie E. Toothacre;Robin H. van der Weide;Claudia D. Lovell;Son C. Nguyen;R. Jordan Barnett;Ashley L. Cook;Han-Seul Ryu;Sarah Pyfrom;Harrison Wang;Daniel Beiting;Jennifer E. Philips-Cremins;Eric F. Joyce;Montserrat C. Anguera - 通讯作者:
Montserrat C. Anguera
Nuclear speckles regulate functional programs in cancer
核斑调节癌症中的功能程序
- DOI:
10.1038/s41556-024-01570-0 - 发表时间:
2025-01-02 - 期刊:
- 影响因子:19.100
- 作者:
Katherine A. Alexander;Ruofan Yu;Nicolas Skuli;Nathan J. Coffey;Son Nguyen;Christine L. Faunce;Hua Huang;Ian P. Dardani;Austin L. Good;Joan Lim;Catherine Y. Li;Nicholas Biddle;Eric F. Joyce;Arjun Raj;Daniel Lee;Brian Keith;M. Celeste Simon;Shelley L. Berger - 通讯作者:
Shelley L. Berger
Multiple allelic configurations govern long-range emShh/em enhancer-promoter communication in the embryonic forebrain
多个等位基因配置控制胚胎前脑中的远程EMSHH/EM Enhancer启动器通信
- DOI:
10.1016/j.molcel.2024.10.042 - 发表时间:
2024-12-19 - 期刊:
- 影响因子:16.600
- 作者:
Jailynn Harke;Jeewon R. Lee;Son C. Nguyen;Arian Arab;Staci M. Rakowiecki;Siewert Hugelier;Christina Paliou;Antonella Rauseo;Rebecca Yunker;Kellen Xu;Yao Yao;Melike Lakadamyali;Guillaume Andrey;Douglas J. Epstein;Eric F. Joyce - 通讯作者:
Eric F. Joyce
Eric F. Joyce的其他文献
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{{ truncateString('Eric F. Joyce', 18)}}的其他基金
Evaluating novel architectural proteins as therapeutic targets for cohesin dysfunction
评估新型结构蛋白作为粘连蛋白功能障碍的治疗靶点
- 批准号:
10593249 - 财政年份:2022
- 资助金额:
$ 40.25万 - 项目类别:
Evaluating novel architectural proteins as therapeutic targets for cohesin dysfunction
评估新型结构蛋白作为粘连蛋白功能障碍的治疗靶点
- 批准号:
10709896 - 财政年份:2022
- 资助金额:
$ 40.25万 - 项目类别:
Regulation of chromatin folding in space and time
染色质折叠在空间和时间上的调节
- 批准号:
10622801 - 财政年份:2018
- 资助金额:
$ 40.25万 - 项目类别:
Regulation of chromatin folding in space and time
染色质折叠在空间和时间上的调节
- 批准号:
10187589 - 财政年份:2018
- 资助金额:
$ 40.25万 - 项目类别:
Regulation of chromatin folding in space and time
染色质折叠在空间和时间上的调节
- 批准号:
10173179 - 财政年份:2018
- 资助金额:
$ 40.25万 - 项目类别:
Exploring the mechanism and function of somatic homolog pairing
探索体细胞同源配对的机制和功能
- 批准号:
8548919 - 财政年份:2011
- 资助金额:
$ 40.25万 - 项目类别:
Exploring the mechanism and function of somatic homolog pairing
探索体细胞同源配对的机制和功能
- 批准号:
8341015 - 财政年份:2011
- 资助金额:
$ 40.25万 - 项目类别:
Exploring the mechanism and function of somatic homolog pairing
探索体细胞同源配对的机制和功能
- 批准号:
8060338 - 财政年份:2011
- 资助金额:
$ 40.25万 - 项目类别:
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