HSF1 granules (green) bind near the chromosome 9 centromere (red).

Upon activation by stress, heat shock factor 1 (HSF1) accumulates at a specific heterochromatic locus on human chromosome 9, according to Jolly et al. (page 775).

The final target of HSF1 is DNA, in the form of the heat shock element (HSE), and this binding event is known to activate transcription of adjacent heat shock protein (hsp) genes. But heat shock also causes HSF1 redistribution into nuclear loci known as HSF1 granules. Jolly and colleagues have now shown that the granules are located at chromosomal DNA sites that are distinct from RNA polymerase II transcription sites, meaning they are unlikely to be related to transcriptional activation. The HSF1 granules were found on the 9q11 region, which is primarily composed of heterochromatic satellite III repeats.

What could transcriptional activators be doing at heterochromatic regions following heat stress? Jolly hypothesizes that heterochromatic localization may provide a buffer to avoid over-activation of HSF1, which can be toxic to the cell. Alternatively, she suggests, the transcription factor may have a secondary role as a protective agent for the locus, preventing damage to a DNA region known to be prone to chromosomal rearrangements. ▪