FIGURE 2.

Model for step wise formation of senescence Heterochromatin foci in aged nuclei. In a young proliferating cell (from left), the Lamin associated domains (LADs) (marked in red), consist of compacted H3K9me3 containing constitutive heterochromatin which are tethered to the nuclear lamina. This constitutive heterochromatin is often flanked by H3K27me3 regions. At the onset of senescence (center), the LADs detach first from the lamina which results in the decondensation of the heterochromatin. This process is followed by the spatial clustering of constitutive heterochromatin to form senescent associated heterochromatin foci. Novel regions in the genome gain Lamin B1, moves towards the periphery to form senescent associated LADs. In addition to this there is global DNA methylation changes. Hypomethylation at the LINEs and SINEs activates the elements and leads to aberrant transcription. The genome further undergoes subsequent redistribution to form the senescent foci. The core structure of the SAHF consists of differential chromatin as depicted in layers (right).