UCR Chemist Part of Team Identifying New Areas of Gene Regulation

Discovery of new location in a key protein that activates genetic activity aided with use of mass spectrometry at UCR

Researcher Kangling Zhang at the University of California, Riverside is part of a team that has discovered a new way that yeast governs genetic expression and repression, a finding that could be repeated in cells of other organisms.

Zhang, an academic coordinator at the Mass Spectrometry Facility of the Department of Chemistry at UCR, worked with Feng Xu and Michael Grunstein of the Department of Biological Chemistry at the David Geffen School of Medicine at UCLA on a paper titled Acetylation in Histone H3 Globular Domain Regulates Gene Expression in Yeast, which was published today in the journal Cell.

The paper focuses on observations of histones, the proteins that regulate genetic expression and form the major supporting structures housing the cell’s DNA. Histones interacting with each other form a ‘spool’ around which DNA is wrapped in the cell. Grunstein, one of the scientists in the current team, discovered in 1991 that sites of histone acetylation, a modification of the protein, play a fundamental role in the regulation of gene activation and repression.

The key findings of the current paper were the discovery of this acetylation at the core of the histone, rather than at the proteins’ ends, which are where most gene regulation is thought to take place. The team used mass spectrometry to show that acetylation at the core of the histone is associated with gene activation by attracting the protein string known as the SWI/SNI chromatin remodeling complex to the location of acetylation.

“In this paper, we used mass spectrometry to identify a novel acetylation site at the lysine 56 of yeast histone H3,” said Zhang, referring to the previously unknown location of a chemical opening to allow genetic transfers to occur. “We found acetylation at this site near the entry-exit points of the DNA superhelix as it wraps around the nucleosome is required for recruiting the nucleosome remodeling complex SWI/SNF and so regulates gene activity,” he said. “We show for the first time that a modification of a histone at the core of the protein, not the end, can regulate genes,” Grunstein added.

The mass spectrometry facility at the UCR’s Department of Chemistry and in the new Physical Sciences building provides super-high sensitivity for research in protein functions and in metabolic profiles of cells. The facility provides service and collaboration not limited to, protein separation, protein identification, sequencing, protein expression level quantification, as well as small molecule structural determination and metabolite identification.