Université Joseph Fourier-Grenoble I, INSERM Institut Albert Bonniot U823, La Tronche, F-38700, France.
Exp Cell Res. 2010 Jul 1;316(11):1845-55. doi: 10.1016/j.yexcr.2010.02.002. Epub 2010 Feb 10.
Cells respond to stress by activating the synthesis of heat shock proteins (HSPs) which protect the cells against the deleterious effects of stress. This mechanism is controlled by the heat shock factor 1 (HSF1). In parallel to HSP gene transcription, in human cells, HSF1 also binds to and transcribes satellite III repeated sequences present in numerous copies in the 9q12 pericentromeric region of chromosome 9. These HSF1 accumulation sites are termed nuclear stress bodies (nSBs). In tumor cells, however, the number of nSBs is higher than the number of 9q12 copies, suggesting the existence of other HSF1 targets. In this paper, we were interested in characterizing these other HSF1 binding sites. We show that HSF1 indeed binds to the pericentromeric region of 14 chromosomes, thereby directing the formation of 'secondary nSBs'. The appearance of secondary nSBs depends on the number of satellite sequences present in the target locus, and on the cellular amount of HSF1 protein. Moreover, secondary nSBs also correspond to transcription sites, thus demonstrating that heat shock induces a genome-wide transcription of satellite sequences. Finally, by analyzing published transcriptomic data, we show that the derepression of these large heterochromatic blocks does not significantly affect the transcription of neighboring genes.
细胞通过激活热休克蛋白（HSPs）的合成来应对应激，这有助于保护细胞免受应激的有害影响。这种机制受热休克因子 1（HSF1）的控制。在人类细胞中，与 HSP 基因转录平行的是，HSF1 还结合并转录存在于 9 号染色体 9q12 着丝粒周围区域大量重复的卫星 III 序列。这些 HSF1 积累位点被称为核应激体（nSBs）。然而，在肿瘤细胞中，nSBs 的数量高于 9q12 拷贝的数量，这表明存在其他 HSF1 靶标。在本文中，我们感兴趣的是表征这些其他 HSF1 结合位点。我们表明 HSF1 确实与 14 条染色体的着丝粒区域结合，从而指导“次级 nSBs”的形成。次级 nSBs 的出现取决于靶基因座中卫星序列的数量以及细胞内 HSF1 蛋白的数量。此外，次级 nSBs 也对应转录位点，从而证明热休克诱导卫星序列的全基因组转录。最后，通过分析已发表的转录组数据，我们表明这些大的异染色质块的去抑制不会显著影响邻近基因的转录。
