South African scientists have proven that some genes "kiss" to switch each other on.
Although "gene kissing" has been hypothesised and many laboratories around the world are striving to demonstrate it, this is the first proof that physical contact is sometimes necessary to activate multiple genes. The research was published in the journal Cell on Thursday.
In each of the about 10-trillion cells in your body, a 1.2m strand of DNA is wrapped like a ball of wool. "So, by default, this compacted DNA is making contact, and genes [which are a portion of DNA] are touching each other," explains Dr Musa Mhlanga, research group leader of the gene expression and biophysics group at the Council for Scientific and Industrial Research (CSIR). "The physical contacts are correlated with gene activity."
Genes provide the code for inherited physical characteristics, such as eye colour, but they also work inside cells to make them function and to keep us alive. The cell switches these genes on or off depending on what it needs. When genes express themselves, they produce ribonucleic acid (RNA).
The question perplexing the international genetics and molecular biology community is: Is the gene activity the cause or the consequence of physical contact?
Research by Mhlanga's group, in collaboration with Professor Marco Weinberg at the University of the Witwatersrand, says that some of these genes have to be touching to be switched on, a departure from our previous understanding that genes are activated by the presence of a transcription factor, which converts DNA to RNA, and by being in the right place at the right time.
"There are many papers describing 3D typology [of genes in a cell], and we know that the organisation is nonrandom," Mhlanga says. When these genes come together, they form a multigene complex, in which they all work together, in an immune or metabolic response, for example.
The researchers looked at three specific genes that cause an inflammation response when activated. "We were able to use molecular scissors to cut the precise position where these genes come into contact … then we looked to see whether the other genes were still able to make RNA and have their gene activity on," Mhlanga says.
Postdoctoral candidate Stephanie Fanucchi, who is part of the CSIR team, says: "Cutting different genes has different effects, and there is a hierarchy in how these genes are being activated, with one master gene and the subordinate genes."
Job Dekker, a professor at the University of Massachusetts Medical School, says the research is impressive. Dekker, who wrote a seminal paper in 2002 detailing a technique to identify and map genes in cells, says: "It really illustrates how much progress we've made in the area of genome engineering. An experiment like this couldn't have been done two years ago" because the techniques available would damage the cell or disrupt the gene activity.
Regarding "gene kissing", these questions are "things people can argue about for years, and all of us have, but we couldn't do anything", Dekker says. "Now, with these methods [such as very sensitive microscopes and molecular scissors, which are enzymes that cut DNA precisely], we can do something."
He expects more discoveries of this kind in the future.
Mhlanga's eyes are also on the future, and he speaks enthusiastically about possible applications of this new know-ledge. "There is another multigene complex that is implicated in breast cancer … Targeting [one of them] may be helpful, but if you want to turn off all the genes implicated in this, you turn off another one [depending on the hierarchy], and it would affect this entire complex."