Recently, some research groups have reported an association between epigenetic regulation and telomere processing: For example, DNA methylation has been indicated as a repressor of telomere recombination, and some chromatin modifications (such as trimethylation of H3K9 and H4K20) are more frequently found in telomere regions. Besides, loss of these heterochromatin marks is linked to abnormal telomere elongation. In this paper, authors showed that telomere lenghts are related to the maintenance of the heterochromatic status of telomeres, using telomerase- null mouse fibroblasts as their model. First -in ChIP experiments- they found that heterochromatic marks (trimethylation of H3K9 and H4K20) decrease, global H4 acetylation increases, and the density of CBX3 (a protein involved in heterochromatin compaction) is lower, as telomeres became shorter, suggesting "an open [chromatin] state as telomere[s...] are lost." No other heterochromatin domains in the genome were associated with this telomere shortening, confirming the specificity of this effect. On the other hand, using bisulfite sequencing they found that subtelomeric regions, that are normally hypermethylated, loss most of this kind of modifications, in relation to this telomere shortening. CO-FISH experiments later showed that telomere- null cells have higher telomere recombination frequencies
In summary, telomere shortening leads to a changes in histone and DNA modifications at mammalian telomeres and subtelomeres characterized by decreased H3K9 and H4K20 trimethylation, increased histone H3 and H4 acetylation and as decreased DNA methylation at subtelomeric repeats, consistent with defective heterochromatin assembly at these regions. [...] Changes in telomeric and subtelomeric modifications in turn could provide a mechanism by which mammalian telomere repeats are counted and autoregulated.Benetti R. et al. 2007. Nature Genet 39(2):243-250
epigenetics
