The regulation of globin gene expression during haematopoiesis

造血过程中珠蛋白基因表达的调控

基本信息

批准号：
MC_UU_00016/4
负责人：
Douglas Higgs
金额：
$ 384.43万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Intramural
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MC_UU_00016%2F4
关键词：
regulation globin gene expression during

项目摘要

We now have an approximate map of the DNA sequence for the entire human genome. However the basic DNA sequence is only a starting block for understanding the complex interplay of factors which regulate the ability of a gene to make the correct protein at the correct time and in the correct cell type. We have a very detailed map of a region of chromosome 16. We want to characterise this region by identifying all the genes and regulatory features within the sequence, and then to look at additional (epigenetic) factors which can influence when and where a gene becomes active. DNA coils down within a cell nucleus with several proteins to form chromatin. We would like to understand how this chromatin is arranged within a nucleus and what changes may be necessary to allow genes to be switched on or off. Within this region of chromosome 16 lie the alpha globin genes. These genes make part of the molecule haemoglobin which carries oxygen in the blood and lack of haemoglobin will give rise to anaemia, which can cause malfunctions in the organs normally supplied with oxygen. When the alpha globin genes are disrupted in some way, patients develop a severe form of anaemia called alpha thalassaemia. Some patients are born with mental retardation and other developmental problems as well as alpha thalassaemia - these patients have a piece of chromosome 16 missing from the region we are studying. With the information from our mapping work and studies of nuclear organisation, we will identify precisely which genes are missing in these patients and how that loss contributes to their mental and developmental difficulties.

现在，我们拥有整个人类基因组的DNA序列的近似图。但是，基本的DNA序列只是理解因子的复杂相互作用的起点，这些因子的复杂相互作用，这些因素调节基因在正确的时间和正确的细胞类型中制作正确蛋白质的能力。我们有一个非常详细的染色体区域图。我们希望通过识别序列中的所有基因和调节特征来表征该区域积极的。 DNA在细胞核中围绕具有几种蛋白质形成染色质的细胞核。我们想了解该染色质是如何在核中排列的，以及允许基因打开或关闭基因的必要变化。在16染色体的该区域中，α球蛋白基因。这些基因使得分子血红蛋白的一部分在血液中携带氧，缺乏血红蛋白会引起贫血，这可能会导致通常含氧的器官中的故障。当α球蛋白基因以某种方式破坏时，患者会发展出一种严重的贫血形式，称为α丘脑贫血。一些患者天生患有智力低下和其他发育问题以及α丘脑贫血 - 这些患者在我们正在研究的地区缺少16号染色体。借助我们对核组织的映射工作和研究的信息，我们将确定这些患者中缺少哪些基因，以及该损失如何影响他们的心理和发育困难。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A gain-of-function single nucleotide variant creates a new promoter which acts as an orientation-dependent enhancer-blocker.

DOI：
10.1038/s41467-021-23980-6
发表时间：
2021-06-21
期刊：
Nature communications
影响因子：
16.6
作者：
Bozhilov YK;Downes DJ;Telenius J;Marieke Oudelaar A;Olivier EN;Mountford JC;Hughes JR;Gibbons RJ;Higgs DR
通讯作者：
Higgs DR

A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions.

DOI：
10.1038/s41467-018-06248-4
发表时间：
2018-09-21
期刊：
Nature communications
影响因子：
16.6
作者：
Brown JM;Roberts NA;Graham B;Waithe D;Lagerholm C;Telenius JM;De Ornellas S;Oudelaar AM;Scott C;Szczerbal I;Babbs C;Kassouf MT;Hughes JR;Higgs DR;Buckle VJ
通讯作者：
Buckle VJ

Super-enhancers require a combination of classical enhancers and novel facilitator elements to drive high levels of gene expression