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

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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.