Functional genomics of an imprinted domain: an integrated model for the epigenetic control of genome function. (360G-Wellcome-086838_Z_08_Z)
Aims of the programme: Genomic imprinting is process causing genes to be expressed according to their parental origin. At mammalian imprinted domains the two parental chromosome homologues function differently despite having the same sequence due to distinct epigenetic modifications on DNA and chromatin, and non-coding transcription that influences parental allele-specific gene expression. Comparing maternally and paternally inherited chromosomes results in genomic imprinting being an excellent paradigm to study cis-regulation and the epigenetic control of transcription in mammalian cells. Here we propose a programme that aims to make links between the underlying DNA sequence, conserved genomic features, epigenetic control, and gene activity and repression at an imprinted domain. Integrated in vivo experiments have been developed, focusing on the 1Mb Dlk1-Dio3 imprinted domain, to address the following key questions: What is the regional influence of large repetitive tracts in ma mmals? (experiment 1) What is the functional importance of physical juxtaposition of long-range cis-acting regulatory interactions? (experiments 2 & 3) Do evolutionary conserved non-coding regions contribute to domain-wide regulation? (experiments 2 & 3) Are large and small non-coding RNA transcripts in the domain, a cause or a consequence of genomic imprinting - what is their role? (experiments 3 & 4)
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Grant Details
Amount Awarded | 676577 |
Applicant Surname | Ferguson-Smith |
Approval Committee | Molecules, Genes and Cells Funding Committee |
Award Date | 2008-11-10T00:00:00+00:00 |
Financial Year | 2008/09 |
Grant Programme: Title | Project Grant |
Internal ID | 086838/Z/08/Z |
Lead Applicant | Prof Anne Ferguson-Smith |
Partnership Value | 676577 |
Planned Dates: End Date | 2011-11-30T00:00:00+00:00 |
Planned Dates: Start Date | 2008-12-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |