In certain cancers, including prostate cancer and lymphomas, members of the Polycomb group (PcG) of proteins appear to abnormally switch genes from on to off, or "silence" them.
The latest work revealed that they do so by placing a small molecule called ubiquitin on a portion of the protein histone H2A, which is tightly associated with DNA.
"This discovery allows greater understanding of how expression of a gene can go awry and may identify a potential target for treatment in certain cancers," said the study's senior author Dr. Yi Zhang, associate professor of biochemistry and biophysics in UNC's School of Medicine and member of the UNC Lineberger Comprehensive Cancer Center.
The new findings appear in the online issue of the journal Nature and will be published in print in October.
Within the cell nucleus, DNA is wrapped tightly around nucleosomes, globular structures composed of four abundant proteins called histones, Zhang said.
"Histone proteins, including H2A, are important in two ways. One is to package genomic material into the nucleus and the other is to regulate processes involving DNA including gene expression, or transcription."
In 1975, histone H2A was the first molecule ever described to be ubiquitinated, or modified by the attachment of the protein ubiquitin, but neither the consequence of H2A ubiquitination nor the molecules responsible were known.
Now, 29 years later, work by Zhang and colleagues has provided answers to both questions.
"Since Polycomb-group proteins have been previously linked to cancer, we anticipate that the ubiquitination of histone H2A will also be linked to some types of cancer," said Zhang.