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Chemical biology approaches to unraveling the histone code

Project description

A new modified peptide-based discovery platform to probe epigenetic regulators

The regulation of gene expression critically modulates genes’ functional roles. Histones are proteins around which DNA is coiled like thread on a spool, giving chromosomes a more compact shape and helping it to fit into the nucleus. A myriad of diverse types of posttranslational modifications of histones and their possible occurrence in various places enables tremendous diversity in the complex networks of highly controlled gene expression programmes. The ERC-funded EPITOOLS project intends to generate new classes of highly selective and potent chemical probes for epigenetic regulators, focusing on enzymes and proteins associated with methyl-lysine marks. Insight could lay the groundwork for therapeutic epigenetic interventions.

Objective

Posttranslational modifications on histones play crucial roles in the epigenetic regulation of eukaryotic gene expression. Chemical modifications that occur on histone tails include acetylation, methylation, phosphorylation, ubiquitination, and SUMOylation. This chemical diversity together with the positions and combinations of these modifications give rise to complex networks of highly controlled gene expression programs. The identification and characterisation of chromatin-associated proteins (or epigenetic regulators) in recent years has advanced our understanding of the significance of these histone modifications and the regulatory outcomes in development and in disease.
The project aims to generate new classes of highly selective and potent chemical probes for epigenetic regulators, focusing on enzymes and proteins associated with methyl-lysine marks. A novel modified peptide-based discovery platform, which combines molecular, chemical, biophysical and cellular techniques, will be developed and applied. These chemical probes will be useful for biological and biomedical research, and will serve as potential starting points for therapeutic epigenetic intervention.

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Coordinator

UNIVERSITY OF NEWCASTLE UPON TYNE
Net EU contribution
€ 964 620,45
Address
Kings gate
NE1 7RU Newcastle upon tyne
United Kingdom

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Region
North East (England) Northumberland and Tyne and Wear Tyneside
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00

Beneficiaries (2)