Colloquium Series: Dr. Steve Henikoff, Fred Hutchinson Cancer Center
MoGen Colloquium Series
Presented by Dr. Steve Henikoff, Fred Hutchinson Cancer Center
Event Details
Monday, March 30, 2026
3:00 pm to 4:00 pm
Naylor Building, Room NL 6
Institution: Fred Hutchinson Cancer Centre, University of Washington School of Medicine
Host
Title:
"Histone overexpression in cancer.”
Abstract:
Genome-wide hypertranscription is common in human cancer and predicts poor prognosis. To understand how hypertranscription might drive cancer, we applied our CUTAC method for mapping RNA polymerase II (RNAPII) genome-wide in formalin-fixed paraffin-embedded (FFPE) sections. RNAPII occupancy at S-phase-dependent histone genes accurately predicted rapid recurrence of meningiomas and corresponded to total whole-arm chromosome losses. Whole-arm losses alone predicted outcome in RNA-sequencing and whole-genome pan-cancer sequencing data. We propose that elevated RNAPII at histone genes both drives hyper-proliferation and displaces the CENP-A histone H3 variant from centromeres, causing centromere breaks and aneuploidies that shape the selective landscape in cancer progenitor cells. Our experimental investigation of the S-phase-dependent histone genes in flies and humans has uncovered a negative feedback loop that regulates histone gene expression over the cell cycle.