Researchers from Fred Hutch Cancer Center and the University of Texas MD Anderson Cancer Center have used a new technique that directly measures gene transcription activity from DNA to show that hyper-elevated levels of RNA Polymerase II (RNAPII) are associated with tumor aggressiveness.
The new technology—Cleavage Under Targeted Accessible Chromatin (CUTAC)—focuses on small, fragmented DNA noncoding sequences where RNAPII bind, located on the same chromosome as the gene they regulate.
When examining clinical samples using CUTAC technology across various cancer types, the researchers found that the expression of histone genes was consistently and significantly higher in tumor samples compared to normal tissue samples.
Histone proteins provide essential structural support for DNA in chromosomes, acting as spools around which DNA strands wrap. These proteins have been well studied, but most current tools to study gene expression rely on RNA sequencing. Histone RNA is unique in that its structure prevents the RNA molecules from being detected by current methods.
“It has been overlooked that histone genes could be a rate-limiting factor in cell replication and, in turn, a strong indicator of tumor cell over-proliferation,” said Ye Zheng, PhD, co-first author and assistant professor of bioinformatics and computational biology at MD Anderson. “This is because current RNA sequencing methods are unable to detect histone RNAs due to their unique structure, meaning these libraries have vastly underestimated their presence. Our novel approach, combining a new experimental technology and computational pipeline, establishes a comprehensive ecosystem that can leverage biopsy samples from multiple cancer types to enhance tumor diagnosis and prognosis.”
