NPCChr · A role for nuclear pore complexes in chromatin organization during early development?
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-03-01 → 2018-04-24
- EU contribution
- €195,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
A role for nuclear pore complexes in chromatin organization during early development?
Cancerous cells proliferate in an uncontrolled manner. However some of these cells are arrested and can not divide anymore. This is called cellular senescence. Senescent cells secrete molecules that can, on one hand reinforce senescence, but on the other hand promote tumour formation – so senescence is considered as a double-edged sword from the persepective of cancer. The genome of senescent cells is organized differently from non senescent cells. The role of this genome reorganization is unclear and we do not know whether it is necessary to arrest cell division. I showed that increase in nuclear pores density is responsible for genome reorganization in senescent cells and explored its role. My results demonstrate that perturbing genome reorganization in senescent cells can maintain cellular arrest but abolishes the secretion of molecules typical of senescent cells, therefore only preserving the anticancerous effect of senescence.
Data: CORDIS, © European Union
Project objective
During differentiation, cells undergo large-scale chromatin rearrangement, notably with the establishment of heterochromatin blocks at the nuclear periphery during the epiblast stage of development. Concomitantly, hundreds of genes are relocated to and from the nuclear periphery and their position is correlated with their expression levels. Most of these genes are associated with regulation of pluripotency, suggesting that the association of fLADs to the NL is a key parameter for proper embryonic development. Recent work of the host lab using synthetic activators showed that the chromatin rearrangement is responsible for the relocation of these genes. However, the mechanisms that govern this chromatin rearrangement are largely unknown. Here I propose to test whether a modulation of nuclear pore density allows chromatin reorganization during differentiation of embryonic stem cells (ESCs) into epiblast stem cells (EpiSCs), laying the groundwork for future analysis in vivo during embryonic development. As a complementary approach, I will determine the mechanisms that prevent heterochromatin formation at nuclear pore complexes. The use of state of the art techniques such as super-resolution microscopy, genome mapping and a multidisciplinary approach combining biology and physics will allow me to understand the role of nuclear pore complexes in the regulation of genome organization.
Original text from CORDIS.
Participants
- THE UNIVERSITY OF EDINBURGH · EdinburghCoordinatorUnited Kingdom
Links
- View on CORDIS
- DOI: 10.3030/655350
- https://arquivo.pt/wayback/20191018133853/https://www.ed.ac.uk:80/igmm
Data: CORDIS, © European Union