In a novel use of gene knockout technology, researchers at the University of California, San Diego School of Medicine tested the same gene inserted into 90 different locations in a yeast chromosome - and discovered that while the inserted gene never altered its surrounding chromatin landscape, differences in that immediate landscape measurably affected gene activity.
The findings, published online in the Jan. 3 issue of Cell Reports, demonstrate that regulation of chromatin - the combination of DNA and proteins that comprise a cell's nucleus - is not governed by a uniform "histone code" but by specific interactions between chromatin and genetic factors.
"One of the main challenges of epigenetics has been to get a handle on how the position of a gene in chromatin affects its expression," said senior author Trey Ideker, PhD, chief of the Division of Genetics in the School of Medicine and professor of bioengineering in UC San Diego's Jacobs School of Engineering. "And one of the major elements of that research has been to look for a histone code, a general set of rules by which histones (proteins that fold and structure DNA inside the nucleus) bind to and affect genes."
The Cell Report findings indicate that there is no singular universal code, according to Ideker. Rather, the effect of epigenetics on gene expression or activity depends not only on the particular mix of histones and other epigenetic material, but also on the identity of the gene being expressed.