Prevention of Chromatin Destabilization by FACT Is Crucial for Malignant Transformation

iScience

卷:23

Eduardo C. Gomez¹  Jianmin Wang¹  Spenser Rosario²  Katerina V. Gurova³  Laura Prendergast³  Alfiya Safina³  Imon Goswami³  Poorva Sandlesh³ 

[1] Department of Bioinformatics, Roswell Park Comprehensive Cancer Center, Carlton and Elm Streets, Buffalo, NY 14127, USA;

[2] Department of Cancer Genetics, Roswell Park Comprehensive Cancer Center, Carlton and Elm Streets, Buffalo, NY 14127, USA;

[3] Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Carlton and Elm Streets, Buffalo, NY 14127, USA;

关键词: Biological Sciences;    Molecular Biology;    Chromosome Organization;    Cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown