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Final Report - TOPONEURONAL (Topoisomerase function in genome and epigenome regulation during neuronal differentiation)

Project ID: 237305
Funded under: FP7-PEOPLE


Transcriptional regulation defines the identity of pluripotent and differentiated cells. DNA Topoisomerases are enzymes that catalyze the unlinking of the DNA strands by making transient DNA strand breaks and allowing the DNA to rotate around these breaks, a process essential for DNA replication, transcription, chromosome condensation and segregation.

The original research proposal aimed at addressing the following key questions:
1) Is Top2ß required for terminal differentiation of embryonic stem cells? Does it contribute to the expression of certain genes?
2) Does it regulate the expression of target genes by directly interacting with genes promoters? What are the genomic sites targeted by Top2ß genomewide? Is there any specific epigenetic signature that associates with these regions?
3) Does Top2ß contribute to transcriptional regulation via regulation of higher order chromatin structure?

As outlined in the report, the project has submitted their work for publication in the peer-reviewed journal Nature Cell Biology under the title 'Topoisomerase IIbeta acts on H3K4 methylated promoters in postmitotic neurons to regulate their differentiation and survival'.

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