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