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Reprogramming the epigenome: erasing memory and creating diversity (360G-Wellcome-210754_Z_18_Z)

<p>Epigenetic memory needs to be globally reprogrammed in the early mammalian embryo for cells to attain broad developmental potency including na&iuml;ve pluripotency. Exit from pluripotency in turn requires rapid establishment of epigenetic memory in the form of epigenetic priming. This involves both &lsquo;activating priming&rsquo; whereby lineage specific genes are protected from repressive marking to safeguard their future transcriptional activation during tissue and organ development, and &lsquo;repressive priming&rsquo; by which genes of a different lineage are suppressed. These large-scale dynamics raise fundamental questions about the impact of epigenetic memory on pluripotency and differentiation, which we address in this research programme. First, we will attempt to disable global demethylation <em>in vitro</em> and <em>in vivo </em>by manipulating the epigenetic coordinator UHRF1 at the transcriptional and posttranscriptional levels. Second, using genetic and epigenetic manipulation we will determine the mechanisms and downstream consequences on lineage and tissue development of &lsquo;activating priming&rsquo; factors we have recently identified. Third, we will investigate the role and targets of &lsquo;repressive priming&rsquo; and epigenetic heterogeneity in cell fate decisions and lineage development. New insights gained into memory erasure and epigenetic determinants of cell fate will illuminate and guide strategies for using ES, iPS, and multipotent stem cells in regenerative medicine.</p>


10 Apr 2018

Grant details
Amount Awarded 2634297
Applicant Surname Reik
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 210754/Z/18/Z
Lead Applicant Prof Wolf Reik
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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