puc-header

Prevention of Chromatin Destabilization by FACT Is Crucial for Malignant Transformation

37 Pages Posted: 18 May 2019 Sneak Peek Status: Under Review

See all articles by Poorva Sandlesh

Poorva Sandlesh

Roswell Park Comprehensive Cancer Center - Department of Cell Stress Biology

Alfiya Safina

Roswell Park Comprehensive Cancer Center - Department of Cell Stress Biology

Imon Goswami

Roswell Park Comprehensive Cancer Center - Department of Cell Stress Biology

Laura Prendergust

Roswell Park Comprehensive Cancer Center - Department of Cell Stress Biology

Spenser Rosario

Roswell Park Comprehensive Cancer Center - Department of Cancer Genetics

Eduardo C. Gomez

Roswell Park Comprehensive Cancer Center - Department of Bioinformatics

Jianmin Wang

Roswell Park Comprehensive Cancer Center - Department of Bioinformatics

Katerina Gurova

Roswell Park Comprehensive Cancer Center - Department of Cell Stress Biology

More...

Abstract

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 cancer patients. 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. While genomic distribution and density of FACT correlated with the intensity of transcription, FACT knockout or knockdown was unexpectedly accompanied by the elevation, rather than suppression, of transcription and with the destabilization of chromatin. These data suggest that the real function of FACT is to stabilize and reassemble nucleosomes disturbed by transcription. This function is apparently vital for tumor cells because malignant transformation is accompanied by chromatin destabilization.

Keywords: Cancer, Chromatin, SSRP1, SPT16, Malignant transformation, transcription, transcription elongation, nucleosome stability, p53, mutant ras, SSRP1 knockout

Suggested Citation

Sandlesh, Poorva and Safina, Alfiya and Goswami, Imon and Prendergust, Laura and Rosario, Spenser and Gomez, Eduardo C. and Wang, Jianmin and Gurova, Katerina, Prevention of Chromatin Destabilization by FACT Is Crucial for Malignant Transformation (May 14, 2019). ISCIENCE-D-19-00456. Available at SSRN: https://ssrn.com/abstract=3388354 or http://dx.doi.org/10.2139/ssrn.3388354
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Poorva Sandlesh

Roswell Park Comprehensive Cancer Center - Department of Cell Stress Biology

Buffalo, NY
United States

Alfiya Safina

Roswell Park Comprehensive Cancer Center - Department of Cell Stress Biology

Buffalo, NY
United States

Imon Goswami

Roswell Park Comprehensive Cancer Center - Department of Cell Stress Biology

Buffalo, NY
United States

Laura Prendergust

Roswell Park Comprehensive Cancer Center - Department of Cell Stress Biology

Buffalo, NY
United States

Spenser Rosario

Roswell Park Comprehensive Cancer Center - Department of Cancer Genetics

Buffalo, NY
United States

Eduardo C. Gomez

Roswell Park Comprehensive Cancer Center - Department of Bioinformatics

Buffalo, NY
United States

Jianmin Wang

Roswell Park Comprehensive Cancer Center - Department of Bioinformatics ( email )

Buffalo, NY
United States

Katerina Gurova (Contact Author)

Roswell Park Comprehensive Cancer Center - Department of Cell Stress Biology ( email )

Buffalo, NY
United States

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
59
PlumX Metrics
Downloads
6