Objective
Topoisomerases are enzymes that solve topological problems arising from DNA templated processes such as replication, transcription, recombination and chromatin remodeling. The type II subfamily of Topoisomerases achieve this task by passing a region of duplex from the same or a different molecule through a double-stranded gap generated in DNA. Mammalian cells encode two isoforms of type II enzymes, Topoisomerase II alpha and beta, which have almost identical enzymatic properties in vitro. However, they show very different expression patterns and it is not known whether they differ in their distribution and action sites on the genome and in gene regulatory potential.
We find that a switch in the expression from Topo II alpha to beta occurs during neuronal differentiation in vitro and in vivo. We propose to define the chromatin crosstalk of the two Topo II isoforms, alpha and beta, and its contribution to the transcriptome of embryonic stem cells and differentiated neurons respectively. We will combine our sophisticated in vitro mouse differentiation system with genome-wide identification of Topo II alpha binding sites in stem cells. These target sequences will be analyzed for any specific features using computational biology tools and related to the existing datasets of various epigenetic modifications and transcription (Tiwari et al. 2011, Nature Genetics). Using Topo II-specific inhibitors, we will identify Topo II alpha target genes that rely on its catalytic activity for their transcription state. We will next compare the Topo II alpha binding data from stem cells to our recently derived genomewide datasets of Topo II beta binding from neurons. Together, we aim to achieve an understanding of the target preference for the two Topo II isoforms, alpha and beta, with respect to sequence features, genomic regions, chromatin profile and transcription state and their dynamics as proliferating, pluripotent stem cells differentiate into postmitotic neurons.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics DNA
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-CIG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
55128 Mainz
Germany
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