Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding

Sayantani Ghosh Dastidar, Bony Kumar, Bo Lauckner, Damien Parrello, Danielle Perley, Maria Vlasenok, Antariksh Tyagi, Nii Koney-Kwaku Koney, Ata Abbas and Sergei Nechaev ()
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Sayantani Ghosh Dastidar: University of North Dakota School of Medicine
Bony Kumar: University of North Dakota School of Medicine
Bo Lauckner: University of North Dakota School of Medicine
Damien Parrello: University of North Dakota School of Medicine
Danielle Perley: University of North Dakota School of Medicine
Maria Vlasenok: University of North Dakota School of Medicine
Antariksh Tyagi: University of North Dakota School of Medicine
Nii Koney-Kwaku Koney: University of North Dakota School of Medicine
Ata Abbas: University of North Dakota School of Medicine
Sergei Nechaev: University of North Dakota School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Responses of cells to stimuli are increasingly discovered to involve the binding of sequence-specific transcription factors outside of known target genes. We wanted to determine to what extent the genome-wide binding and function of a transcription factor are shaped by the cell type versus the stimulus. To do so, we induced the Heat Shock Response pathway in two different cancer cell lines with two different stimuli and related the binding of its master regulator HSF1 to nascent RNA and chromatin accessibility. Here, we show that HSF1 binding patterns retain their identity between basal conditions and under different magnitudes of activation, so that common HSF1 binding is globally associated with distinct transcription outcomes. HSF1-induced increase in DNA accessibility was modest in scale, but occurred predominantly at remote genomic sites. Apart from regulating transcription at existing elements including promoters and enhancers, HSF1 binding amplified during responses to stimuli may engage inactive chromatin.

Date: 2023
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DOI: 10.1038/s41467-023-43157-7

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