Structure and function of SRA domains implicated in chromatin regulation

在多细胞生物体中，所有细胞都以DNA的形式继承相同的遗传信息。DNA中的信息通常被解码以制造蛋白质或RNA。随着生物体的发育，一些细胞会将特定的DNA序列(基因)解码成蛋白质和RNA，而其他细胞则不会。近年来，人们对参与这一过程的不同分子有了大量的了解。通常，特定的蛋白质结合在特定DNA序列(基因)的开头附近以启动解码；这些蛋白质被称为转录因子，它们识别并结合到特定的基因。然而，细胞内的DNA与结构蛋白(称为组蛋白)捆绑在一起。最近，人们已经清楚地看到，这种包装可以由蛋白质以一种基因特异性的方式控制。我们怀疑DNA的包装可能会导致特定的序列被隐藏在复杂的结构中，从而不再进行解码。这可以比作阅读一本书，在这本书中，可以阅读的内容由在特定页面打开的书控制。目前，人们正在非常深入地研究控制这种“页面阅读”的几种机制。我们的目标是研究一类在DNA包装水平上以某种方式参与基因转录调控的蛋白质。它们是如何工作的还不清楚，但我们迄今进行的研究已经提供了一个假说，我们可以从这个假说开始进一步探索。我们打算研究的这类蛋白质的一个重要特征是，它们与许多伴侣相互作用，形成一个功能齐全的蛋白质复合体。我们计划确定特定构建块(蛋白质结构域)的结构，然后研究它如何与关键伙伴蛋白质相互作用。利用这些信息，我们将进行进一步的实验，旨在直接跟踪体内的相互作用，并确定该结构域在复合体中如何发挥作用来调节DNA包装。

In a multi-cellular organism all cells inherit the same genetic information in the form of DNA. The information in the DNA is typically decoded to make proteins or RNA. As the organism develops some cells will decode particular DNA sequences (genes) into proteins and RNA, whilst other cells will not. In recent years a great deal has been learnt about the different molecules, which are involved in carrying out this process. Typically, specific proteins bind near the beginning of a particular DNA sequence (gene) to initiate the decoding; these proteins are called transcription factors and they recognise and bind to particular genes. However, the DNA within the cell is packaged in bundles with structural proteins (called histones). Recently, it has become clear that this packaging can be controlled by proteins in a gene-specific manner. We suspect that the packaging of the DNA can lead to particular sequences being hidden away inside a complex structure so that decoding no longer occurs. This may be likened to reading a book where what can be read is controlled by whatever opens the book at particular pages. Several mechanisms for the control of this 'page reading' are now being studied very intensively. We aim to study a class of proteins that are in some way involved in the regulation of gene transcription at this level of DNA packaging. How they work is not yet clear, but the studies that we have carried out so far have provided a hypothesis from which we can begin to explore further. An important feature of the class of proteins we intend to study is that they interact with many partners to form a fully functional protein complex. We are planning to determine the structure of a particular building block (a protein domain) and then study how it interacts with key partner proteins. Using this information we will then carry out further experiments designed to follow directly the interactions in vivo and establish how this domain functions within the complex to regulate DNA packaging.