An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

To understand how heterochromatin acts at the molecular level, we are looking at the effect of abrogating important heterochromatic activities, such as histone and/or DNA methyl-transferases, on the overall composition of key heterochromatic loci (telomeres, pericentromeres and rDNA). In particular, we are interested in: 

(i) How telomere compositional changes upon loss of heterochromatin function can explain the appearance of the ALT (Alternative Lengthening of Telomeres) pathway observed in certain cancers. 

(ii) How the situation at ALT telomeres can be compared to the changes observed at human satellite 2 sequences upon loss of DNA methylation in ICF cells. Indeed, satellite 2 regions recombine aberrantly and localize to PML bodies in ICF cells, a "behavior" also observed in the case of ALT telomeres. 

(iii) How pericentric heterochromatin is regulated by such enzymatic activities during development, differentiation and why such regulation matters for genome stability.

(iv) Characterizing a new heterochromatin protein which possibly links DNA methylation and non-coding RNAs.

(v) How is rDNA expression regulated?