MetEor: Metastable Epialleles on Request
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Background

Both mouse experiments and human epidemiological investigations indicate that the effects of lifestyle and environmental challenges can be transmitted through non-genetic mechanisms across generations. In mouse there is compelling evidence that repetitive elements are able to mediate this. The Agouti viable yellow (Avy)[1] and Axin Fused (AxinFu)[2] loci are both naturally occurring mutant mice where the insertion of an endogenous retrovirus (ERV) within the locus produces phenotypic range in either coat colour (Avy)[3] or tail morphology (AxinFu)[4] that correlates with methylation levels.

These regions are termed “Metastable Epialleles”[5] and are characterised by:

  1. Stable intra-individual methylation levels between tissues.
  2. Variable inter-individual methylation levels within the population.

We have recently identified 45 metastable epialleles (MEs) in the C57BL/6 mouse strain[6]. MetEoR provides an interactive browser that allows the user to investigate the location of MEs within the genome and perform interactive analytics with epigenetic data including methylomes, histone modifications and CTCF binding data. In addition, MetEoR also allows the user to view the underlying pyrosequencing validation data for each ME, providing information on the methylation range identified at each locus.

Project Aims

Species and strains to be included:

Species Strain
Mus_musculus C57BL6
Mus_musculus CAST
Homo_sapiens

Further Reading

  1. Dickies, M.M. (1962). A new viable yellow mutation in the house mouse. J. Hered. 53, 84–86.
  2. Vasicek, T.J., Zeng, L., Guan, X.J., Zhang, T., Costantini, F. and Tilghman, S.M. (1997). Two dominant mutations in the mouse fused gene are the result of transposon insertions. Genetics 147, 777–786.
  3. Michaud, E.J., van Vugt, M.J., Bultman, S.J., Sweet, H.O., Davisson, M.T. and Woychik, R.P. (1994). Differential expression of a new dominant agouti allele (Aiapy) is correlated with methylation state and is influenced by parental lineage. Genes Dev. 8, 1463–1472.
  4. Rakyan, V.K., Chong, S., Champ, M.E., Cuthbert, P.C., Morgan, H.D., Luu, K.V. and Whitelaw, E. (2003). Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc. Natl. Acad. Sci. USA 100, 2538–2543.
  5. Rakyan, V.K., Blewitt, M.E., Druker, R., Preis, J.I., and Whitelaw, E. (2002). Metastable epialleles in mammals. Trends Genet. 18, 348–351.
  6. Kazachenka A., Bertozzi T.M., Sjoberg-Herrera M.K., Walker N., Gardner J., Gunning R., Pahita E., Adams S., Adams D., Ferguson-Smith A.C. (2018) Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance. Cell. 2018 Nov 29;175(6):1717. DOI

Contact

github.com/darogan/MetEor_Project

www.gen.cam.ac.uk/research-groups/ferguson-smith