Genomic imprinting and the epigenetic control of developmental processes

基因组印记和发育过程的表观遗传控制

• 批准号: MR/J001597/1
• 负责人: Anne Ferguson-Smith
• 金额: $ 189.09万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ001597%2F1
• 关键词: Genomic; imprinting; epigenetic; control; developmental

A large number of serious diseases, including type2 diabetes and cancer, are caused by a combination of our genetic make-up (our DNA) and environmental influences. We believe that our DNA can be directly influenced by the environment in which it finds itself. Sometimes the effect of the environment is part of normal change that a cell goes through. In particular we study how the environment influences how DNA is normally packaged into chromosome inside the cell. This process of DNA packaging is not haphazard but highly regulated and is different between young cells and old cells, brain cells and muscle cells. Understanding how the environment signals to cells and causes them to become abnormal is a difficult problem to address. One way to do this is to study a system where cells normally have to respond to their environment and change their behavior. A good system to investigate in this is through the study of cells known as stem cells, that are changing in the normal process of developing into body parts such as the brain, fat or muscles. These developing cells are good models because these are the types of cells that can go wrong in cancer so results generated from studying them in normal development can be compared with results generated when they are behaving abnormally. Here we will study the relationship between the DNA and the regulatory processes that package it into chromosomes while stem cells are developing. We will learn how this affects the behavior of genes encoded by the DNA and what happens to these genes in different cell types and in different environments.

大量严重疾病，包括2型糖尿病和癌症，是由我们的基因组成（我们的DNA）和环境影响的组合引起的。我们认为，我们的DNA可以直接受到发现自己的环境的影响。有时环境的效果是单元通过的正常变化的一部分。特别是我们研究环境如何影响DNA通常包装到细胞内的染色体中。 DNA包装的过程不是随意的，而是高度调节的，在幼小细胞，脑细胞和肌肉细胞之间也有所不同。了解环境如何向细胞发出信号并使它们变成异常是一个困难的问题。一种方法是研究一个通常需要对其环境做出反应并改变其行为的系统。在此过程中进行调查的一个很好的系统是通过研究称为干细胞的细胞的研究，这些细胞正在正常发展为大脑，脂肪或肌肉等正常的过程中变化。这些开发细胞是良好的模型，因为这些是癌症中可能出错的细胞类型，因此可以将它们在正常发育中研究产生的结果与表现异常产生的结果进行比较。在这里，我们将研究干细胞发展时DNA与将其包装成染色体的调节过程之间的关系。我们将学习这如何影响由DNA编码的基因的行为，以及在不同细胞类型和不同环境中这些基因会发生什么。

项目成果

Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells.

• DOI: 10.1038/ncomms10458
• 发表时间: 2016-01-29
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Butcher LM;Ito M;Brimpari M;Morris TJ;Soares FAC;Ährlund-Richter L;Carey N;Vallier L;Ferguson-Smith AC;Beck S
• 通讯作者: Beck S

A co-ordinated transcriptional programme in the maternal liver supplies LC-PUFAs to the conceptus using phospholipids

• DOI: 10.1101/2023.06.23.546226
• 发表时间: 2023-06
• 期刊: bioRxiv
• 作者: Risha Amarsi;S. Furse;M. A. Cleaton;Sarah Maurel;Alice L Mitchell;A. Ferguson-Smith;N. Cenac;C. Williamson;A. Koulman;M. Charalambous

Epigenetic control of the genome-lessons from genomic imprinting.

• DOI: 10.3390/genes5030635
• 发表时间: 2014-08-14
• 期刊: Genes
• 影响因子: 3.5
• 作者: Adalsteinsson BT;Ferguson-Smith AC
• 通讯作者: Ferguson-Smith AC

Defective folate metabolism causes germline epigenetic instability and distinguishes Hira as a phenotype inheritance biomarker.

• DOI: 10.1038/s41467-021-24036-5
• 发表时间: 2021-06-17
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Blake GET;Zhao X;Yung HW;Burton GJ;Ferguson-Smith AC;Hamilton RS;Watson ED
• 通讯作者: Watson ED