Periodic Reporting for period 3 - IDRE (IMPACT OF DNA REPLICATION ON EPIGENETICS)
Okres sprawozdawczy: 2020-05-01 do 2021-10-31
One of the ways cells control whether genes are turned ‘on’ or ‘off’ is by placing epigenetic tags on their DNA molecule. But when cells are dividing, these tags are removed, meaning they need to be put back once cells have finished dividing. Our aim is to identify and understand the mechanisms cells use to put these tags back in the right place after cells have divided. It is a fundamental question in cell biology since if these tags are lost, cells lose their identity as it is the case during tumorigenesis. It also sheds light on how decisions are taken during development, from a single cell (zygote) to a full organism composed of 200 different cell types.
They key objective of this project is to develop technologies to understand the dynamic of chromatin restoration in cycling cells. We combine in vivo labelling of newly replicated DNA and mass spectrometry analysis. We show that a large proportion of chromatin-based processes are profoundly affected by the DNA replication machinery. These processes include transcription and 3D nuclear architecture.
They key objective of this project is to develop technologies to understand the dynamic of chromatin restoration in cycling cells. We combine in vivo labelling of newly replicated DNA and mass spectrometry analysis. We show that a large proportion of chromatin-based processes are profoundly affected by the DNA replication machinery. These processes include transcription and 3D nuclear architecture.
Two important goals have been reached: 1) We have analyzed the composition of chromatin throughout the cell cycle in cancer cells and the maintenance of histone modifications through the cell cycle in mES cells. 2) We have developed the Nascent Chromatin Capture in non-cancer and human IPS cells. This is central to start the next step and address the questions regarding chromatin plasticity and developmental choices.
Development of the technology in human IPS has been faster than expected thanks to the recruitment of a postdoctoral researcher with previous expertise in human IPS cells. We will therefore be able to finish our plan on time and hope to discover new mechanisms dictating cell fate. Moreover, because we are using human IPS cells, it opens up fantastic opportunities to boost our understanding of the reprogramming process.