TET protein function in conversion of 5mC to 5hmC during cell cycle entry

人类细胞中被称为基因的DNA部分通过一个称为转录的过程进行复制（该拷贝称为mRNA），也称为基因表达。每个mRNA的序列提供了单个蛋白质的蓝图。每一种mRNA被细胞“读取”，产生每一种蛋白质的许多拷贝，然后改变细胞在体内的作用。我们正在研究血液中一种称为T细胞的细胞，它有助于对抗感染，改变T细胞中表达的mRNA会影响它的作用。DNA位于细胞核中，长约3米。它被称为组蛋白的蛋白质结合。组蛋白包裹并扭曲DNA，将其压缩10，000倍，使其适合细胞的中间，称为细胞核。这些组蛋白的位置也控制着基因如何转录成mRNA。人体内的一些细胞，如干细胞和T细胞处于静止状态，称为静止。重要的是保持这些细胞静止，直到身体发出信号让它们分裂并被激活。我们发现，有一个调节点，称为承诺点，T细胞必须被刺激通过这个控制点才能承诺增殖。当这些静止细胞受到刺激时，大量基因被诱导，这对于确保细胞增殖和活化正确发生至关重要。我们有证据表明，当T细胞开始增殖时，DNA发生了一种称为5hmC的修饰，我们认为这可能是因为诱导了一种称为“泰特”的蛋白质。我们知道，5hmC修饰决定了某些基因是否可以转录。本项目将研究我们的假设，即当T细胞开始增殖时，由泰特形成的5hmC在调节某些基因的转录中是重要的。这很重要，因为我们相信这将是一种新的机制，可以调节我们免疫系统中非常重要的细胞。

Parts of the DNA of human cells known as genes are copied (the copy is called an mRNA) by a process known as transcription, also known as gene expression. The sequence of each mRNA provides the blueprint for an individual protein. Eeach mRNA is "read" by the cell to produce many copies of each protein that then alter what the cell can do in the body. We are studying a type of cell in the blood called a T cell that helps to fight infection and changing the mRNAs that are expressed in T cells affects how it does this. The DNA is in the nucleus of the cell and it is about 3 metres long. It is bound by proteins called histones. The histones wrap and twist the DNA to compact it 10,000-times so it fits into the middle of the cell, called the nucleus. The position of these histones also controls how genes are transcribed into mRNA. Some cells in the body, such as stem cells and T cells are in a resting state called quiescence. It is important to keep these cells quiescent until the body signals them to divide and become activated. We showed that there is a regulatory point, called the commitment point and T cells have to be stimulated past this control point in order to become committed to proliferate. When these quiescent cells are stimulated a large number of genes are induced, which is critical for ensuring that cell proliferation and activation occur correctly. We have evidence that a modification to the DNA, called 5hmC occurs when the T cells start to proliferate and we think this may occur because proteins called "TET" are induced. We know that the 5hmC modification determines whether some genes can be transcribed or not. This project will investigate our hypothesis that formation of 5hmC by TET as T cells start to proliferate is important in regulating the transcription of some genes. This is important as we believe that this will be a new mechanism that regulates a very important cell of our immune system.