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Homeodomain transcription factors in vertebrates: working together to make a difference

脊椎动物中的同源域转录因子：共同努力发挥作用

基本信息

批准号：
BB/N00907X/1
负责人：
Nicoletta Bobola
金额：
$ 98.63万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FN00907X%2F1
关键词：
Homeodomain transcription factors vertebrates working

项目摘要

How do different anatomical features develop with remarkable precision along the body axis of each animal species? We know that this process is determined by a group of proteins belonging to the Hox family. The Hox proteins read and execute instructions encoded in the genome. Each member of the Hox family appears in a well-defined territory of the developing embryo, and recognises specific instructions (most likely DNA sequences) contained in the genome. A puzzling finding is that the Hox specificity, which is central to developmental programs, is entirely lost in a test tube, where all Hox proteins recognise similar DNA sequences. Thus some other essential unknown biochemical factor must be present in the developing embryo. This project will identify Hox functional targets in the genome, and thus reveal the mechanisms that allow Hox proteins to control anatomical development. We will apply state-of-the-art experimental technologies and develop new computational methods to investigate systems where Hox proteins control development and their malfunctioning causes disease. Collectively, these results will identify the fundamental mechanisms that underlie anatomical development in vertebrates and will cast light on how their malfunctioning can result in diseases.

不同的解剖特征是如何沿着每个动物物种的身体轴线以惊人的精度发展的？我们知道这个过程是由一组属于Hox家族的蛋白质决定的。Hox蛋白读取并执行基因组编码的指令。Hox家族的每个成员都出现在发育中的胚胎的一个明确的领域，并识别基因组中包含的特定指令（很可能是DNA序列）。一个令人困惑的发现是Hox特异性，这是发育程序的核心，在试管中完全丢失，所有Hox蛋白识别相似的DNA序列。因此，在发育中的胚胎中一定存在着其他一些重要的未知生化因素。该项目将确定基因组中Hox的功能靶点，从而揭示Hox蛋白控制解剖发育的机制。我们将应用最先进的实验技术并开发新的计算方法来研究Hox蛋白控制发育及其故障导致疾病的系统。总的来说，这些结果将确定脊椎动物解剖发育的基本机制，并将阐明它们的故障是如何导致疾病的。

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）

Uncovering tissue-specific binding features from differential deep learning

DOI：
10.1101/606269
发表时间：
2019-04
期刊：
Nucleic Acids Research
影响因子：
14.9
作者：
Mike Phuycharoen;P. Zarrineh;Laure Bridoux;Shilu Amin;Marta Losa;Ke Chen;N. Bobola;M. Rattray
通讯作者：
Mike Phuycharoen;P. Zarrineh;Laure Bridoux;Shilu Amin;Marta Losa;Ke Chen;N. Bobola;M. Rattray

From DNA binding to transcriptional activation: Is the TALE complete?