The role of spatial nuclear organisation ingenome function

空间核组织基因组功能的作用

• 批准号: MC_UU_00007/2
• 负责人: Wendy Bickmore
• 金额: $ 475.28万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00007%2F2
• 关键词: role; spatial; nuclear; organisation; ingenome

The linear sequence map of the DNA that makes up our human genome is an incomplete description of our genetic information. This is because information on genome function and gene regulation is also encoded in the way that the DNA sequence is folded up with proteins within chromosomes and within the cell nucleus. Our work tries to understand the three-dimensional folding of the genome, and how this controls how our genome functions in normal development and how this may be perturbed in disease. A particularly important question is how genes are controlled in time and space by elements in our genome called enhancers that can located far away from the genes that they control. This is an important area of human genetics because most of the common genetic variation between individuals in a population that affects our life-time risk of developing disease, lies in enhancers. A prominent feature of our work is the use of visual assays to investigate how the genome is folded up. To do this we combine fluorescence in situ hybridisation (FISH) and digital microscopy with the use of automated image analysis software.

构成人类基因组的DNA线性序列图是对我们遗传信息的不完整描述。这是因为基因组功能和基因调控的信息也是以DNA序列与染色体内和细胞核内的蛋白质折叠的方式编码的。我们的工作试图了解基因组的三维折叠，以及它如何控制我们的基因组在正常发育中的功能，以及它如何在疾病中受到干扰。一个特别重要的问题是，基因是如何在时间和空间上被我们基因组中被称为增强子的元件控制的，这些元件可以位于远离它们控制的基因的地方。这是人类遗传学的一个重要领域，因为影响我们终身患病风险的群体中个体之间的大多数常见遗传变异都存在于增强子中。我们工作的一个突出特点是使用视觉分析来研究基因组是如何折叠的。为此，我们结合联合收割机荧光原位杂交（FISH）和数字显微镜与自动图像分析软件的使用。

项目成果

Quantitative spatial and temporal assessment of regulatory element activity in zebrafish.

• DOI: 10.7554/elife.65601
• 发表时间: 2021-11-19
• 期刊: eLife
• 影响因子: 7.7
• 作者: Bhatia S;Kleinjan DJ;Uttley K;Mann A;Dellepiane N;Bickmore WA
• 通讯作者: Bickmore WA

A Central Role for Canonical PRC1 in Shaping the 3D Nuclear Landscape

Canonical PRC1 在塑造 3D 核景观方面的核心作用

• DOI: 10.1101/2019.12.15.876771
• 发表时间: 2019
• 作者: Boyle S

MUC4 is not expressed in cell lines used for live cell imaging.

• DOI: 10.12688/wellcomeopenres.17229.2
• 发表时间: 2021
• 期刊: Wellcome open research
• 作者: Athmane N;Williamson I;Boyle S;Biddie SC;Bickmore WA
• 通讯作者: Bickmore WA