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Chromatin mediated control of retrotransposons

Reference	BB/E014445/1
Principal Investigator / Supervisor	Dr Simon Whitehall
Co-Investigators / Co-Supervisors
Institution	Newcastle University
Department	Inst for Cell and Molecular Biosciences
Funding type	Research
Value (£)	287,394
Status	Completed
Type	Research Grant
Start date	01/10/2007
End date	30/09/2010
Duration	36 months

Abstract

The expression of endogenous retrotransposons is tightly controlled as this is thought to be one mechanism that limits the potentially deleterious spread of these elements. While a number of studies have analysed the expression of retrotransposons at a global level there is very limited information relating to the regulation of individual elements. Therefore, we are currently using the fission yeast, Schizosaccharomyces pombe as a model system to analyze the regulation of individual retrotransposable elements. Our preliminary studies indicate that the basal expression of Tf2 retrotransposable elements is dependent upon their chromosomal context. Furthermore, the expression of at least a subset of these elements is repressed by the HIR/Asf1 nucleosome assembly factors and histone deacetylases suggesting that chromatin plays a key role in the regulation of these elements. Therefore, major objectives of this study are to dissect the regulatory mechanisms that control the expression of individual Tf2 elements and to characterise the chromatin structures that are associated with these elements. Further objectives are to determine whether disruption of chromatin leads to the mobilization of Tf2 retrotransposons and because retrotransposable elements are potential sources of genomic instability, to determine the role that chromatin plays in suppressing ectopic recombination between Tf2 elements.

Summary

Retrotransposons are mobile genetic elements which are found in the genomes of all eukaryotic organisms including humans. They are structurally and functionally related to retroviruses such as HIV and have the potential to be very harmful to the host organism because they may disrupt genes, alter their expression and can also drive genomic rearrangements. Indeed, occasionally retrotransposons can cause genetic disease and so all organisms must carefully control the expression of such elements. Therefore, the aims of this work are firstly, to study the mechanisms that control the expression of retrotransposons and secondly, to determine the outcomes when these controls are impaired. Retrotransposons that are related to those present in humans are also found in simple organisms such as yeast. Therefore, this study will use the fission yeast to study the control of retrotransposons as this unicellular organism is much easier to study and manipulate than complex multicellular organisms such as a humans.

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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