There was an interesting session on epigenetics at ASCB this evening. Epigenetics is a term with a slippery definition, but it is basically the study of changes to the way the genome is managed that are heritable but generally don’t affect the genome sequence itself. A lot of research in this area looks at the histone proteins around which DNA wraps, and the specific chemical modifications that can be made to them that in turn appear to affect gene expression in a persistent way.
One talk by David Katz, a postdoc at Emory focused on specific modifcations made to histones in the germline of an organism – that is the cells that become eggs or sperm and lead to future offspring. Katz works with Caenorhabditis elegans, a roundworm. He looked at methylation on Histone H3. Apparently in developing C. elegans practically every cell shows a good deal of methylation of H3 at the fourth lysine residue (K4). H3K4 is not methylated in the germ cells. Without methylation at this specific spot, the genes that wrap around the histones are more likely to be silenced, which is normal for germ cells. They won’t be needed for a while, so why express them. So, Katz looked to see what happened if he disrupted a so-called demethylase gene that removes these methyl marks. It appeared to have absolutely no effect in the first generation, but after following more than 20 generations of the mutant worms, he noticed that their fertility was dropping off to the point that by the 26th generation (if I saw the graph correctly) the worms are practically sterile. Their oogenesis was highly abnormal. If these results are easily confirmed it is another powerful statement for the effects epigenetic changes might have on the germline over a number of generations, a startling testament to the sometimes slow and subtle effects of epigenetics on reproductive health.
A talk later in the evening focused on histone variants associated with DNA damage and how they co-localize with other DNA damage associated proteins. Unfortunately, however, her powerpoint presentation failed to show any red coloured figures. I’ve never seen anyone’s presentation get so derailed by a technical difficulty. Green spots that revealed the location of one DNA repair protein showed up fine, but the red spots that were supposed to show us where the histones appeared in the cell simply weren’t there. It was impossible to understand what she was trying to show. Eventually she got the presentation working. An Apple computer apparently got her back on track, apparently. But during the minor meltdown, someone behind me commented to a colleague, “Now you know what it’s like to be red/green colour blind.” It is amazing to me that so many people present microarray heat maps and cell biological information in red and green with out considering the 7% to 10% of folks (almost all of them male) that can’t distinguish the two.