SAHF

SAHF stands for senescence-associated heterochromatin foci, a set of densely packed chromatin regions that form within the nucleus of many senescent cells. SAHF are observed in several models of cellular senescence, including replicative and oncogene-induced senescence, particularly in human fibroblasts, but they are not universal to all senescent cells.

Formation and composition: SAHF appear as DAPI-dense foci and are enriched for heterochromatin-associated marks such as H3K9me3 and H4K20me3. They often contain histone variants like macroH2A and chromatin proteins such as HP1. The assembly of SAHF is linked to the activation of the RB pathway and recruitment of chromatin remodeling factors that promote a repressive chromatin state. Through this reorganization, portions of the genome are condensed into discrete blocks, contributing to the silencing of proliferation-related genes, including many E2F targets.

Function and significance: The proposed function of SAHF is to reinforce a stable cell cycle arrest by enforcing a repressive chromatin environment on genes required for cell division. However, SAHF are not strictly required for senescence in all contexts, and some senescent cells do not form SAHF. Their presence or absence can reflect cell type, the inducer of senescence, and the chromatin landscape of the cell. In cancer biology, SAHF have been studied as a component of the senescence program that can act as a barrier to tumorigenesis, though their exact role is context-dependent.

Detection and limitations: SAHF are typically detected by fluorescence microscopy, using DNA stains like DAPI to visualize dense foci, often complemented by immunostaining for heterochromatin marks or HP1. Because SAHF formation varies with cell type and inducer, they are one of several chromatin-based readouts of senescence.