Sandlesh Poorva, Safina Alfiya, Goswami Imon, Prendergast Laura, Rosario Spenser, Gomez Eduardo C, Wang Jianmin, Gurova Katerina V
Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Carlton and Elm Streets, Buffalo, NY 14127, USA.
Department of Cancer Genetics, Roswell Park Comprehensive Cancer Center, Carlton and Elm Streets, Buffalo, NY 14127, USA.
iScience. 2020 Jun 26;23(6):101177. doi: 10.1016/j.isci.2020.101177. Epub 2020 May 18.
Histone chaperone FACT is commonly expressed and essential for the viability of transformed but not normal cells, and its expression levels correlate with poor prognosis in patients with cancer. FACT binds several components of nucleosomes and has been viewed as a factor destabilizing nucleosomes to facilitate RNA polymerase passage. To connect FACT's role in transcription with the viability of tumor cells, we analyzed genome-wide FACT binding to chromatin in conjunction with transcription in mouse and human cells with different degrees of FACT dependence. Genomic distribution and density of FACT correlated with the intensity of transcription. However, FACT knockout or knockdown was unexpectedly accompanied by the elevation, rather than suppression, of transcription and with the destabilization of chromatin in transformed, but not normal cells. These data suggest that FACT stabilizes and reassembles nucleosomes disturbed by transcription. This function is vital for tumor cells because malignant transformation is accompanied by chromatin destabilization.
组蛋白伴侣FACT在转化细胞而非正常细胞中普遍表达且对其生存能力至关重要，其表达水平与癌症患者的不良预后相关。FACT与核小体的多个组分结合，并且一直被视为一种使核小体不稳定以促进RNA聚合酶通过的因子。为了将FACT在转录中的作用与肿瘤细胞的生存能力联系起来，我们结合不同程度依赖FACT的小鼠和人类细胞中的转录情况，分析了全基因组范围内FACT与染色质的结合。FACT的基因组分布和密度与转录强度相关。然而，意外的是，在转化细胞而非正常细胞中，FACT基因敲除或敲低伴随着转录的升高而非抑制，以及染色质的不稳定。这些数据表明，FACT可稳定并重新组装因转录而受到干扰的核小体。该功能对肿瘤细胞至关重要，因为恶性转化伴随着染色质不稳定。
