HISTONESTEM · Histone arginine methylation and citrullination in stem cell maintenance and specification
FP7 — People (Marie Curie Actions)
- Duration
- 2010-07-01 → 2012-06-30
- EU contribution
- €240,290
- Participants
- 1
- Scheme
- MC-IEF
Lines connect the coordinator with its partners.
Results in brief
Histone arginine methylation and citrullination in stem-cell maintenance and specification
In this project, we intended to investigate the role of histone arginine citrullination in the maintenance of the pluri / multipotency status of mouse embryonic stem cells and neural stem cells, and in the specification of neural stem cells, namely into the oligodendrocyte lineage. Using techniques such as chromatin / ribonucleic acid (RNA) immunoprecipitation, coupled with quantitative polymerase chain reaction (PCR) or next-generation sequencing and stable isotope labelling by amino acids in cell culture (SILAC) technology, coupled with immunoprecipitation and mass spectrometry, amongst others, we were able to identify new roles for histone citrullination in pluripotency, and in particular in cellular reprogramming. We were also able to identify novel interactors of the transcription factors Sox2, which might reveal novel mechanism of actions for this protein. Increased understanding of the epigenetic regulation of stem cell fate is of uttermost importance for the development of cell therapies. Our results provide mechanistic insights and highlight novel players in the transcriptional regulation of pluripotency. Our results could be useful for the generation of pluripotent cells, for instance through reprogramming of somatic cells.
Data: CORDIS, © European Union
Project objective
Transcription in any given cell type is regulated at the level of chromatin, the complex where all nuclear DNA is packaged together with histones. Post-translational modifications at arginine and lysine residues of histones are key regulators of transcription. Furthermore, histone arginine methylation and citrullination appear to be important in the transcriptional control of several developmental processes. In this project, I intend to investigate the role of histone arginine methylation and citrullination in: (1) the maintenance of the pluri/multipotency status of mouse embryonic stem cells and neural stem cells; (2) the specification of neural stem cells, namely into the oligodendrocyte lineage. Increased understanding of the epigenetic regulation of stem cell fate and oligodendrocyte development is of uttermost importance for the development of cell therapies, in particular for demyelinating diseases. This interdisciplinary project will take advantage of my previously acquired expertise in stem cell biology and neural development, and of the host laboratory’s expertise in epigenetics, chromatin and transcription. I will be using leading-edge techniques such as chromatin immunoprecipitation (ChIP) – sequencing and Stable Isotope Labelling by Aminoacids in Cell culture (SILAC) technology, among others. Thus, this project will allow me to get research training in state-of-the-art techniques in the epigenetics field, which will be essential for my plans to become a principal investigator in the area of epigenetic regulation of neural development, with a focus on oligodendrogenesis.
Original text from CORDIS.
Participants
- THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGECoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union