In epigenomics, location is everything: Researchers exploit gene position to test 'histone code'

Jan 03, 2013
This is an X-ray micrograph of a yeast cell, Saccharomyces cerevisiae, as it buds before dividing. Credit: Carolyn Larabell, UC San Francisco, Lawrence Berkeley National Laboratory and the National Institute of General Medical Sciences.

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 – the combination of DNA and proteins that comprise a cell's nucleus – is not governed by a uniform "" but by specific interactions between chromatin and .

"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.

To show this, the researchers exploited an overlooked feature of an existing resource. The widely-used gene knockout library for yeast, originally created to see what happens when a particular gene is missing, was built by systematically inserting the same reporter gene into different locations. Ideker and colleagues focused on this and observed what happens to gene expression at different locations along yeast .

"If epigenetics didn't matter – the state of histones and DNA surrounding the gene – the expression of a gene would be the same regardless of where on the chromosome that gene is positioned," said Ideker. But in every case, was measurably influenced by interaction with nearby epigenetic players.

Ideker said the work provides a new tool for more deeply exploring how and why genes function, particularly in relation to their location.

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JVK
1 / 5 (2) Jan 03, 2013
Diamond, Binstock and Kohl (1996) "The Genome, positioning, timings. Increasingly the structure and timings within the nucleus are realized as contributing to gene expression regulation.

Molecular distance. As measured in centimorgans, human and other species' male and female chromosomes, including the autosomes, tend to have different lengths in various segments. To some extent, this suggests a correlation with physical distance but instead the differing lengths are based upon rates of recombination; although sections of most female chromosomes are longer than their homologous counterparts in male chromosomes, in some segments of various chromosomes opposite length-difference occurs, with males having larger centimorgan values than females in those regions. While ramifications of these centimorgan sexual dimorphisms are not yet clearly established..." http://www.hawaii...ion.html
PPihkala
1 / 5 (1) Jan 04, 2013
It should be common knowledge now that chromosome's position in nucleus correlates with it's activity level. Therefore it should be no surprise if gene's location within chromosome also modulates activity.

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