Enhancer function and dysfunction: molecular mechanisms, genome context, and disease

增强子功能和功能障碍：分子机制、基因组背景和疾病

• 批准号: MC_UU_00035/7
• 负责人: Wendy Bickmore
• 金额: $ 603.21万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00035%2F7
• 关键词: Enhancer; function; dysfunction; molecular; mechanisms

The complexity of our development, health and disease is dependent on the precise way that our genes are controlled. This is driven by genetic switches embedded in the 95% of our genome that does not contain genes – the so-called non-coding genome. Mutations in these switches can cause severe disease but we do not understand how. This programme aims to investigate how the three-dimensional folding of the genome underpins how these genetic switches work and to improve our understanding of how genetic changes in these genetic elements contributes to disease and disease risk.

我们的发育、健康和疾病的复杂性取决于我们控制基因的精确方式。这是由嵌入在我们基因组中95%不包含基因的基因开关驱动的——即所谓的非编码基因组。这些开关的突变可能导致严重的疾病，但我们不知道其中的原因。该计划旨在研究基因组的三维折叠如何支撑这些遗传开关的工作方式，并提高我们对这些遗传元素的遗传变化如何导致疾病和疾病风险的理解。

项目成果

Unique activities of two overlapping PAX6 retinal enhancers.

两个重叠的PAX6视网膜增强剂的独特活动。

• DOI: 10.26508/lsa.202302126
• 发表时间: 2023-11
• 期刊: LIFE SCIENCE ALLIANCE
• 影响因子: 4.4
• 作者: Uttley, Kirsty;Papanastasiou, Andrew S.;Lahne, Manuela;Brisbane, Jennifer M.;Macdonald, Ryan B.;Bickmore, Wendy A.;Bhatia, Shipra
• 通讯作者: Bhatia, Shipra

Short-read whole genome sequencing identifies causative variants in most individuals with previously unexplained aniridia.

短读长全基因组测序可识别大多数患有先前无法解释的无虹膜的个体的致病变异。

• DOI: 10.1136/jmg-2023-109181
• 发表时间: 2023
• 期刊: Journal of medical genetics
• 影响因子: 4
• 作者: Hall HN

Ultra-long-range interactions between active regulatory elements.

• DOI: 10.1101/gr.277567.122
• 发表时间: 2023-08
• 期刊: GENOME RESEARCH
• 影响因子: 7
• 作者: Friman, Elias T;Flyamer, Ilya M;Marenduzzo, Davide;Boyle, Shelagh;Bickmore, Wendy A
• 通讯作者: Bickmore, Wendy A

Expansion of ventral foregut is linked to changes in the enhancer landscape for organ-specific differentiation.

• DOI: 10.1038/s41556-022-01075-8
• 发表时间: 2023-03
• 期刊: NATURE CELL BIOLOGY
• 影响因子: 21.3
• 作者: Wong, Yan Fung;Kumar, Yatendra;Proks, Martin;Herrera, Jose Alejandro Romero;Rothova, Michaela Mrugala;Monteiro, Rita S.;Pozzi, Sara;Jennings, Rachel E.;Hanley, Neil A.;Bickmore, Wendy A.;Brickman, Joshua M.
• 通讯作者: Brickman, Joshua M.

Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops.

• DOI: 10.26508/lsa.202302101
• 发表时间: 2023-10
• 期刊: LIFE SCIENCE ALLIANCE
• 影响因子: 4.4
• 作者: Williamson, Iain;Boyle, Shelagh;Grimes, Graeme R.;Friman, Elias T.;Bickmore, Wendy A.
• 通讯作者: Bickmore, Wendy A.