Understanding the mechanisms that suppress the transcription of the non-coding genome

通过基因转录过程对我们的基因组进行解码，最终决定了我们体内细胞的形式和活动。然而，为了正确地进行这一过程，我们的基因组需要以正确和适当的方式在空间上进行组织。为了维持这种空间组织，被称为转座子的小片段DNA需要保持不活跃，我们的细胞有几台机器被设计来控制这些转座子的活动。未能灭活转座子可能会导致我们基因组空间连接的混乱后果，并导致细胞身份的变化。我们最近发现了这些机器的一个新组件，称为ZMYM2，它在我们的细胞中扮演着重要的角色，使它们能够保持自己的身份。ZMYM2功能的破坏会导致遗传的肾脏疾病，当与不同的蛋白质结合时也可能导致癌症。人们对这种蛋白质在分子水平上的功能知之甚少，在这里，我们将填补这一知识空白。具体地说，我们将研究ZMYM2如何影响基因组的折叠和沉默反转录转座子的机器的招募。我们还将研究ZMYM2函数中的“相分离”现象。相分离是指分子以类似液体的状态结合在一起，这有助于细胞过程的区隔。我们的发现对于理解细胞状态是如何通过抑制反转录转座子活性来维持的将是重要的。

The decoding of our genome through the process of gene transcription ultimately dictates the form and activity of the cells in our body. However, for this to proceed correctly, our genome needs to be spatially organised in a correct and appropriate manner. To maintain this spatial organisation, small pieces of DNA known as transposons need to be kept inactive and our cells have several machines that are designed to keep the activity of these transposons in check. Failure to inactivate transposons can cause chaotic consequences for the spatial wiring of our genome and result in changes to cellular identity. We recently identified a new component of these machines known as ZMYM2 which plays an important role in our cells, allowing them to maintain their identity. Disruption of ZMYM2 function leads to genetically inherited kidney disorders and can also lead to cancer when combined with a different protein. Little is known about how this protein functions at the molecular level and here we will fill this knowledge gap. Specifically we will study how ZMYM2 affects the folding of the genome and the recruitment of machines that function to silence retrotransposons. We will also study the phenomenon of "phase separation" in ZMYM2 function. Phase separation relates to when molecules become associated in a liquid-like state that helps with compartmentalisation of cellular processes. Our findings will be important for understanding how cell states are maintained through the suppression of retrotransposon activity.