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.

许多严重的疾病，包括2型糖尿病和癌症，都是由我们的基因组成（我们的DNA）和环境影响共同造成的。我们相信，我们的DNA可以直接受到它所处环境的影响。有时环境的影响是细胞正常变化的一部分。特别是，我们研究了环境如何影响DNA在细胞内正常包装成染色体的方式。这种DNA包装过程不是偶然的，而是高度受调控的，并且在年轻细胞和老年细胞，脑细胞和肌肉细胞之间是不同的。了解环境如何向细胞发出信号并导致它们变得异常是一个难以解决的问题。一种方法是研究一个系统，在这个系统中，细胞通常必须对环境做出反应并改变它们的行为。一个很好的研究系统是通过研究被称为干细胞的细胞，这些细胞在发育成身体部位（如大脑，脂肪或肌肉）的正常过程中发生变化。这些发育中的细胞是很好的模型，因为这些细胞类型在癌症中可能会出错，因此研究它们正常发育时产生的结果可以与它们行为异常时产生的结果进行比较。在这里，我们将研究干细胞发育过程中DNA与将其包装成染色体的调控过程之间的关系。我们将了解这如何影响DNA编码的基因的行为，以及这些基因在不同的细胞类型和不同的环境中会发生什么。

项目成果

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

非CG DNA甲基化是用于评估多能干细胞中内胚层分化能力的生物标志物。

• 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

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

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