The analysis of epigenetic modifications at the level of the genome is a very promising field of research. The major question to be addressed is how the epigenome distinguishes cell types and how epigenetic variability between individuals reflects the influence of the environment and might relate to phenotypic diversity and susceptibility to diseases.
By using cutting-edge technologies to map DNA methylation genome-wide (MeDIP-ChIP), we will first identify sites of promoter DNA methylation that distinguish cell lineages in both human and mouse and study the reprogramming of promoter DNA methylation during development. Second, using a mouse model, we will test whether these developmentally regulated patterns of DNA methylation are altered by exposure to environmental pollutants such as Endocrine Disruptors (EDs) and possibly transmitted over multiple generations.
Guibert S, Forne T, Weber M (2009). Dynamic regulation of DNA methylation during mammalian development. Epigenomics 1:81-98.
Borgel J., Guibert S., Li Y., Chiba H., Schübeler D., Sasaki H., Forné T. and Weber M. (2010). Targets and dynamics of promoter DNA methylation during early mouse development. Nature Genetics. 42, 1093-1100.
Bonilla E, del Mazo J (2010). Deregulation of the Sod1 and Nd1 genes in mouse fetal oocytes exposed to mono-(2-ethylhexyl) phthalate (MEHP). Reprod Toxicol 30:387-92.
Auclair G, Weber M (2012). Mechanisms of DNA methylation and demethylation in mammals. Biochimie 94:2202-11.
Borgel J, Guibert S, Weber M (2012). Methylated DNA Immunoprecipitation (MeDIP) from low amounts of cells. Methods Mol Biol, 925:149-58.
López-Casas PP, Mizrak SC, López-Ferní¡ndez LA, Paz M, de Rooij DG, del Mazo J (2012).The effects of different endocrine disruptors defining compound-specific alterations of gene expression profiles in the developing testis. Reprod Toxicol 33:106-15.
Amandine Henckel, Karim Chebli, Satya K Kota, Philippe Arnaud and Robert Feil (2012). Transcription and histone methylation changes correlate with imprint acquisition in male germ cells. EMBO J 31:606-615.
Borgel J., Guilbert S. and Weber M. (2012). Methylated DNA immunoprecipitation (MeDIP) from low amounts of cells. Methods in Molecular Biology. 925, 149-58.
Guibert S., Forné T. and Weber M. (2013). Global profiling of DNA methylation erasure in mouse primordial germ cells. Genome Research 22:633-41.
Brieño-Enríquez M A, García-López J, Cí¡rdenas DB, Guibert S, DÄ›d L, Hourcade JdD, PÄ›knicoví¡ J, Weber M, del Mazo J. Prenatal exposure to endocrine disruptors induces trans-generational deregulation of microRNAs involved in the Lin28-let-7-Blimp1 pathway in male primordial germ cells, in preparation.