Mammalian telomeres have epigenetic marks of constitutive
heterochromatin. Here, we study the impact of telomere length
on the maintenance of heterochromatin domains at telomeres.
Telomerase-deficient Terc–/– mice with short telomeres show
decreased trimethylation of histone 3 at Lys9 (H3K9) and
histone 4 at Lys20 (H4K20) in telomeric and subtelomeric
chromatin as well as decreased CBX3 binding accompanied
by increased H3 and H4 acetylation at these regions.
Subtelomeric DNA methylation is also decreased in
conjunction with telomere shortening in Terc–/– mice. In
contrast, telomere repeat factors 1 and 2 show normal binding
to telomeres independent of telomere length. These results
indicate that loss of telomeric repeats leads to a change in
the architecture of telomeric and subtelomeric chromatin
consisting of loss of heterochromatic features leading to a
more ‘open’ chromatin state. These observations highlight the
importance of telomere repeats in the establishment of
constitutive heterochromatin at mammalian telomeres and
subtelomeres and point to histone modifications as important
in counting telomere repeats.
