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R-loop coupled chromatin regulation (360G-Wellcome-210654_Z_18_Z)

Non-canonical chromatin structures are emerging as important components of gene regulation. One example, RNA-DNA hybrid structures known as R-loops, occur frequently in many genomes. Initially studied with respect to genome instability, they have now been linked to transcriptional regulation, heterochromatin formation and recombination. But exactly what regulates R-loop dynamics, and how R-loops influence local chromatin states to affect a wide range of chromatin processes is still poorly understood. Deriving mechanistic understanding of R-loops from genome wide analyses is difficult. We will therefore focus on one functionally important R-loop and exploit a genetically tractable system and a wealth of information to develop deep mechanistic understanding into the regulation and role of an R-loop. We will identify novel factors that stabilize and resolve the R-loop, and establish how their functions are integrated. We will investigate whether the R-loop sets up a transcription-replication conflict that propagates heterochromatinization of the locus, thus setting the expression state. We will also dissect if R-loop dynamics and a gene loop influence promoter dominance to co-ordinate sense and antisense transcription. Active collaborations will enable a broad set of approaches to be used and concepts to be compared between organisms.


10 Apr 2018

Grant details
Amount Awarded 1449786
Applicant Surname Dean
Approval Committee Science Interview Panel
Award Date 2018-04-10T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Investigator Award in Science
Internal ID 210654/Z/18/Z
Lead Applicant Prof Dame Caroline Dean
Planned Dates: End Date 2023-10-01T00:00:00+00:00
Planned Dates: Start Date 2018-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
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