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Transgenerational epigenetic inheritance: mechanisms and consequences for metabolism and ageing

Reference	BBS/E/B/000C0424
Principal Investigator / Supervisor	Dr Gavin Kelsey
Co-Investigators / Co-Supervisors	Dr Maria Casanueva, Dr Maria Christophorou, Dr Myriam Hemberger, Dr Jonathan Houseley, Dr Peter Rugg-Gunn
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	1,650,793
Status	Current
Type	Institute Project
Start date	01/04/2017
End date	31/03/2023
Duration	59 months

Abstract

Epigenetic changes that occur during the lifetime of an individual are generally not inherited by the next generation, as this could subvert epigenetic reprogramming events needed to reinstate totipotency. Yet, some genomic elements remain incompletely reprogrammed, and may thus represent a key genomic vehicle for transgenerational epigenetic inheritance47. Transgenerational inheritance requires that the germline remembers exposure to environmental changes and allows for these to be inherited to the next generation(s). Nutritional stress can mediate transgenerational memory through histone marks and small RNA pathways in invertebrates and DNA methylation changes in mice48,49. As observed in many studies, the inheritance mediated by epigenetic modifications reverts back to wild-type after one or a few generations. However, some epigenetic changes can lead to more permanent genome rearrangements, when coupled to genomic instability. For example, nutritional stress can lead to instability of high copy number ribosomal DNA (rDNA), resulting in copy number variation (CNV) at rDNA loci. There are many key aspects that remain unresolved in the field and this Objective tackles two essential questions: firstly, what are the mechanisms by which epigenetic reprogramming normally returns cells to a naïve and totipotent stage and could these mechanisms thereby mediate transgenerational inheritance upon experimental manipulation. Secondly, can, and if so how could, stressors such as age and nutrition contribute to inheritance by modifying CNV through gametes with consequences for metabolism and ageing in subsequent generations.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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