List of gene promoters studied.

<p>List of gene promoters studied.</p

Age-related DNA methylation patterns at imprinted gene promoters in cerebral cortex.

<p>DNA methylation status in cerebral specific CpG sites within promoters of imprinted genes in young i.e., 6 months (a) and old i.e., 27 months (b) C57BL/6 mice. Each tickmark represents specific CpG sites within the imprinted promoter and each column represents the methylation status for each animal.</p

Age-related DNA methylation patterns at imprinted and non-imprinted gene promoters in liver.

<p>DNA methylation status in liver at specific CpG sites within promoters of imprinted genes of young, i.e. 6 months (a) and old, i.e. 27 months (b) C57BL/6 mice liver. Each tickmark represents specific CpG sites within the imprinted promoter and each column represents the methylation status for each animal.</p

DNA methylation patterns at imprinted and non-imprinted gene promoters in <i>Ku80^−/−</i> mutant mice.

<p>DNA methylation status in liver at specific CpG sites within promoters of imprinted genes of <i>WT</i> (a) and <i>Ku80^−/−</i> (b) mice liver (both 10 months of age). Each tickmark represents specific CpG sites within the imprinted promoter and each column represents the methylation status for each animal.</p

Age-related DNA methylation patterns at non-imprinted gene promoters in cerebral cortex.

<p>DNA methylation status in cerebral cortex at specific CpG sites within promoters of non-imprinted genes of young, i.e. 6 months (a), and old, i.e. 27 months (b), C57BL/6 mice. Each tickmark represents specific CpG sites within the non-imprinted promoter and each column represents the methylation status for each animal.</p

DNA methylation patterns at imprinted and non-imprinted gene promoters in <i>Ercc-/d7</i> mutant mice.

<p>DNA methylation status in liver at specific CpG sites within promoters of imprinted genes of <i>WT</i> (a) and <i>Ercc-/d7</i> (b) mice liver (both 14 weeks of age). Each tickmark represents specific CpG sites within the imprinted promoter and each column represents the methylation status for each animal.</p

EpiGram tab for the gene Mkrn3.

<p>The EpiGram is a graphical representation of methylation ratios found in each sample for the amplicon studied. Each sample’s nucleotide sequence is displayed as a series of individual CpGs, which are color-coded columns on the same line. The color within the column denotes the level of methylation found at this particular site in the selected sample. The color spectrum ranges from yellow (or 0% methylated) CpG units to blue (100% methylated) CpG units. Grey dots denote not analyzable CpG sites. Above an example of an EpiGram obtained for the studied imprinted gene Mkrn3. The first 10 lines are relative to the five WT samples (in duplicates), lines 11 to 20 are relative to the Ku80^−/− samples. The last line corresponds to the unmethylated sample, used as a conversion control. Some CpG sites (i.e. CpG sites 2–3, 8–9, 14–18) were analyzed as “units” (i.e. ≥1 CpG site) because of their close vicinity to each other in the sequence.</p

Histopathology neoplastic lesions.

<p>Mentioned n-numbers are tumor bearing animals available for microscopical examination.</p><p><i>k</i>-/-;<i>d</i>-/-: <i>ku80</i>-/-; <i>dna-pk_cs^−/−</i>.</p><p>mes. lm. nd.: mesenterial lymph node.</p><p>ax. lm. nd.: axillary lymph node.</p><p>*∼5 thymus tumor preparations were microscopically examined per group and found to be all lymphomas. All other macroscopic neoplastic lesions observed in thymus are assumed to be lymphomas as well.</p><p>** analyzed in femur.</p><p>Tumor incidence based on all animals from longevity cohort, including those not microscopically examined.</p

Breeding strategy to generate the knockout cohorts.

<p><i>Ku80^+/−</i> and <i>dna-pk_cs</i>^+/− animals are backcrossed for multiple generations to C57Bl6/J-pUR288 (left of dashed line) and FVB (right of dashed line) background. Double heterozygous knock out C57BL6/J male mice are crossed with double heterozygous knock out FVB female mice. Using this strategy all four desired cohorts are generated as F1 hybrids (grey boxes).</p

Survival curves.

<p>Median survivals are shown in the figure legends in parentheses. <i>dna-pk_cs^−/−</i> mice live significantly longer compared to <i>ku80^−/−</i> mice in both male (<i>p</i> = 0.01) and females (<i>p</i> = 8.7*10⁻⁶) mice. Survival of double knock out mice is identical to <i>ku80^−/−</i>. (A) Males. (B) Females.</p