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Role of ncRNAs in Chromatin and Transcription

Objective

The human genome is highly transcribed, with over 90% of sequences contributing to the production of RNA. The function of the vast majority of these RNAs is unknown. Evidence over many years has revealed that transcription factors and chromatin regulators are associated with a variety of non-coding (nc)RNAs, but their function remains largely unknown. There are a few cases where a role has been ascribed for ncRNAs in transcription, but no clear mechanistic insight has been defined yet. We predict that many of the newly identified ncRNAs emanating from the genome will play a role in transcriptional processes. We intend to identify and characterise such ncRNAs. This will take place in two phases. In the first phase we will use biochemical approaches to identify ncRNAs involved in the regulation of chromatin and transcription. Our investigations will focus on proteins leading to the induction of pluripotency and oncogenesis. ncRNAs associated with such proteins will be identified using targeted screens. In the second phase, the importance of these RNAs in determining pluripotency and oncogenesis will be analysed. In addition, a variety of molecular approaches will be used to investigate the mechanism by which these ncRNAs regulate the function of the proteins or complexes they associate with. One particular hypothesis we will explore is that such ncRNAs play a role in guiding proteins to DNA sequences, via the formation of RNA/DNA triplexes. This concerted and focused analysis will provide mechanistic insights into the functions of ncRNAs in transcriptional regulation and validate their role in key biological processes. The identification of such new ncRNA-regulated pathways may open up new avenues for therapeutic intervention.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/rna
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/genetics and heredity/genome

Call for proposal

ERC-2010-AdG_20100317
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Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 063 187
Principal investigator
Tony Kouzarides (Prof.)
Administrative Contact
Renata Schaeffer (Ms.)

Beneficiaries (2)

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 2 063 187
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments
Principal investigator
Tony Kouzarides (Prof.)
Administrative Contact
Renata Schaeffer (Ms.)
THE RESEARCH FOUNDATION OF STATE UNIVERSITY OF NEW YORK
United States
EU contribution
€ 78 282,80
Address
State Street 35
12201 Albany Ny
Activity type
Other
Administrative Contact
Bethan Large (Ms.)