UNDERSTANDING THE INTERPLAY OF ENHANCERS, CHROMATIN PRIMING ELEMENTS AND SIGNALS REGULATING DYNAMIC GENE EXPRESSION IN DEVELOPMENT

了解增强子、染色质启动元件和发育过程中动态基因表达调节信号的相互作用

• 批准号: BB/R014809/1
• 负责人: Constanze Bonifer
• 金额: $ 99.09万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=BB%2FR014809%2F1
• 关键词: UNDERSTANDING; INTERPLAY; ENHANCERS; CHROMATIN; PRIMING

The formation of a fully functional organism during embryonic development is primarily coordinated and controlled by extra-cellular signalling modulators and regulators of gene expression. A fascinating aspect of embryonic development is that the timing of how different cells form is always the same. The reason for this synchrony is that all information for our body plan is encoded in our DNA, which contains instructions on when our genes should be expressed and when they should be silent. Moreover, developing cells communicate via signals to synchronize their development and activate genes to produce proteins, called transcription factors which can "read" the genetic code. These factors work together with many other proteins to ensure that genes are expressed in the right cell and at the right time. However, our DNA is packaged into a compact structure called chromatin which on the one hand ensures that it fits into the nucleus, but on the other hand restricts transcription factor access. How chromatin structure, transcription factors and signals work together to properly regulate gene expression is unclear. To answer this question, we will use an in vitro differentiation system that mimics normal development in vitro. We will collect data on all genes, and we will use computational biology methods to answer the fundamental question of how the balance and timing of gene expression are controlled in development.

在胚胎发育过程中，功能齐全的生物体的形成主要是由细胞外信号调节剂和基因表达调节剂协调和控制的。胚胎发育的一个迷人的方面是，不同细胞形成的时间总是相同的。这种同步的原因是，我们身体计划的所有信息都编码在我们的DNA中，其中包含关于我们的基因何时应该表达以及何时应该沉默的指令。此外，发育中的细胞通过信号进行通信，以同步它们的发育，并激活基因产生蛋白质，称为转录因子，可以“读取”遗传密码。这些因子与许多其他蛋白质一起工作，以确保基因在正确的细胞中和正确的时间表达。然而，我们的DNA被包装成一个紧凑的结构，称为染色质，一方面确保它适合细胞核，但另一方面限制转录因子的访问。染色质结构、转录因子和信号如何共同作用以适当地调节基因表达尚不清楚。为了回答这个问题，我们将使用一种模拟体外正常发育的体外分化系统。我们将收集所有基因的数据，我们将使用计算生物学方法来回答基因表达的平衡和时间在发育中如何控制的基本问题。

项目成果

A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification.

• DOI: 10.1038/s41467-023-35910-9
• 发表时间: 2023-01-17
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Edginton-White, B.;Maytum, A.;Kellaway, S. G.;Goode, D. K.;Keane, P.;Pagnuco, I.;Assi, S. A.;Ames, L.;Clarke, M.;Cockerill, P. N.;Gottgens, B.;Cazier, J. B.;Bonifer, C.
• 通讯作者: Bonifer, C.

A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification

信号响应增强子的全基因组中继驱动造血规范

• DOI: 10.1101/2022.03.22.485307
• 发表时间: 2022
• 作者: Edginton-White B

Chromatin priming elements direct tissue-specific gene activity prior to hematopoietic specification

染色质启动元件在造血规范之前指导组织特异性基因活性

• DOI: 10.1101/2023.08.30.555485
• 发表时间: 2023
• 作者: Maytum A

Identification and characterization of enhancer elements controlling cell type-specific and signalling dependent chromatin programming during hematopoietic development.

• DOI: 10.21037/sci-2023-011
• 发表时间: 2023
• 期刊: Stem cell investigation