Epigenetic inheritance – models and mechanisms

1 June 2023, 4.00 PM - 1 June 2023, 5.00 PM

Professor Anne Ferguson-Smith (Pro-Vice-Chancellor for Research and International Partnerships, University of Cambridge)

OS6 Oakfield House and online

Hosted by the Medical Research Council (MRC) Integrative Epidemiology Unit (IEU)

Abstract: Epigenetic modifications to DNA and chromatin influence chromosome architecture, gene regulation and the silencing of transposable elements. Epigenetic changes have been associated with responses to environmental perturbations, and diseases such as cancer. In mammals, epigenetic modifications are not generally heritable from one generation to the next, yet environmentally induced phenotypes observed in one generation can be observed in the next, and mechanisms conferring such effects are not understood.   

Genomic imprinting is a process causing genes to be expressed according to their parental origin and is regulated by epigenetic marks transmitted from one generation to the next. Mechanisms regulating the inheritance of genomic imprints are well-understood and can be compared with other models of proposed epigenetic inheritance where similarities and differences can be considered.   

In particular, inter-individual variability in transposable element methylation has been linked to phenotypic diversity, environmental adaptability, and transgenerational epigenetic inheritance, however, the molecular mechanisms underlying this in mammals remain unknown. We identified a repertoire of murine variably methylated retrotransposons (VM-TEs) in mouse and characterised their properties, heritability and response to environmental insult.  Variable methylation states are highly susceptible to genetic background effects which we have used to identify regulators of inter-individual methylation variability and their role in the regulation of these states within and across generations.  Our experiments also indicate that epigenetic inheritance at VM-TEs is the exception rather than the rule. Our findings encouraged us to revisit the heritability of the classic paradigm of intergenerational epigenetic inheritance at the Agouti viable yellow locus and preliminary findings will be presented.  

Bio: Professor Anne Ferguson-Smith is the Pro-Vice-Chancellor for Research and International Partnerships at the University of Cambridge. She is the Arthur Balfour Professor of Genetics (since 2015). Formerly, she was the University’s Head of the Department of Genetics until December 2020. She became the President of the Genetics Society in 2021, and is a member of the UKRI BBSRC Council.   

Professor Ferguson-Smith is a mammalian developmental geneticist and epigeneticist. An expert on genomic imprinting, her team studies the epigenetic control of genome function with particular emphasis on epigenetic inheritance. Her group is made up of both experimental and computational scientists and current research focuses on three themes: (i) stem cells and the epigenetic programme, (ii) functional genomics and epigenomics, and (iii) the interaction between the environment and development, health and disease within and across generations.   

She was elected to EMBO in 2006, to the UK Academy of Medical Sciences and the Society of Biology in 2012, and became a Fellow of the Royal Society in 2017. In 2014 she was as awarded the Women in Science Heirloom Award for contributions to life sciences, In 2019 she was awarded the Feldberg Prize and in 2021 the Buchanan Medal and the Society for Reproduction and Fertility, Anne McLaren Distinguished Scientist Award. Professor Ferguson-Smith became Pro-Vice-Chancellor for Research in 2021 and was appointed to the Research and International Partnerships role in 2022. She is a Fellow of Darwin College, University of Cambridge.  

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