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RNA polymerase II at histone genes predicts outcome in human cancer
Dr Ye Zheng, University of Texas MD Anderson Cancer Center
April 14 @ 1:00 pm – 2:00 pm
This is an online event held via Zoom: https://uni-sydney.zoom.us/j/85114748391
Genome-wide hypertranscription is common in human cancer and predicts poor prognosis. To understand how hypertranscription might drive cancer, we applied our formalin-fixed paraffin-embedded (FFPE)–cleavage under targeted accessible chromatin method for mapping RNA polymerase II (RNAPII) genome-wide in FFPE sections. We demonstrate global RNAPII elevations in mouse gliomas and assorted human tumors in small clinical samples and discover regional elevations corresponding to de novo HER2 amplifications punctuated by likely selective sweeps. RNAPII occupancy at S-phase-dependent histone genes correlated with WHO grade in meningiomas, accurately predicted rapid recurrence, and corresponded to whole-arm chromosome losses. Elevated RNAPII at histone genes in meningiomas and diverse breast cancers is consistent with histone production being rate-limiting for S-phase progression and histone gene hypertranscription driving overproliferation and aneuploidy in cancer, with general implications for precision oncology.
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Dr Ye Zheng
Ye Zheng is a tenure-track Assistant Professor in the Bioinformatics and Computational Biology Department of the University of Texas MD Anderson Cancer Center and an NIH/NHGRI K99/R00 fellow. Dr. Zheng received her postdoctoral training at the Fred Hutchinson Cancer Center from both molecular biology and quantitative modeling perspectives mentored by Dr. Steven Henikoff. Before her postdoctoral training, Dr. Zheng received a Ph.D. in Statistics from the University of Wisconsin-Madison under the supervision of Dr. Sündüz Keleş. At MD Anderson Cancer Center, Dr. Zheng leads a hybrid research group. Her quantitative research group is dedicated to the statistical modeling and computational pipeline development using bulk and single-cell transcriptomics, proteomics, epigenomics, and 3D genomics data to address biological and clinical challenges. Her wet lab specializes in the epigenomic profiling of the Formalin-Fixed, Paraffin-Embedded (FFPE) samples.