Understanding how mammalian genomes are packaged in complex chromatin structures. (360G-Wellcome-078219_Z_05_Z)

£512,274

Studying chromatin is essential to understanding fundamental cellular processes that act on DNA, such as transcription, replication and repair and how it affects many human diseases. Although we have a clear understanding of the structure of the nucleosome we know very little about higher levels of chromatin folding or how it is regulated. The chromatin architecture of mammalian genomes is heterogeneous and I have previously shown that the gene-rich regions of the human genome have a more open higher-order chromatin conformation than gene-poor regions. Constitutive heterochromatin is molecularly distinct from euchromatin. I have shown that both human and mouse satellite-containing centromeric heterochromatin has a compact higher-order chromatin structure. In this proposal I aim to identify factors responsible for regulating the conformation of the chromatin fibre in heterochromatin and examine their mechanism of action. Using a biophysical assay I will determine whether histone and DNA modifications have the capacity to alter the conformation of the chromatin fibre. Using a further development of this technique to purify centromeric heterochromatin, I will examine whether the higher-order 30nm chromatin fibre has a structural RNA component that can modulate its conformation, and will identify new protein components of the chromatin fibre.

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Grant Details

Amount Awarded 512274
Applicant Surname Gilbert
Approval Committee Basic Science Interview Committee
Award Date 2005-12-13T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Research Career Development Fellowship
Internal ID 078219/Z/05/Z
Lead Applicant Prof Nick Gilbert
Partnership Value 512274
Planned Dates: End Date 2010-05-31T00:00:00+00:00
Planned Dates: Start Date 2006-06-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland
Sponsor(s) Prof David Porteous