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Publication : Prevention of Chromatin Destabilization by FACT Is Crucial for Malignant Transformation.

First Author  Sandlesh P Year  2020
Journal  iScience Volume  23
Issue  6 Pages  101177
PubMed ID  32498018 Mgi Jnum  J:306964
Mgi Id  MGI:6717728 Doi  10.1016/j.isci.2020.101177
Citation  Sandlesh P, et al. (2020) Prevention of Chromatin Destabilization by FACT Is Crucial for Malignant Transformation. iScience 23(6):101177
abstractText  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.
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