Tangled up in Keystone

A funny thing happened to the Keystone symposium on epigenetics and development, apparently a few years back it got invaded by chromatin people. At my first day at the symposium, I uncovered just a little grumbling that the histone modifications that control the winding and packing of DNA and that ultimately grant or restrict access to transcriptional machinery don?t quite qualify as epigenetic marks. The players in the field have yet to demonstrate that they are heritable said Ueli Grossniklaus of the University of Zurich as we chatted at the evening poster session. Nevertheless, it?s hard not to get excited about the possibility that there is an underlying language of histone modifications: acetylation, methylation, and phosphorylation on specific sites of histone tails that appear to serve as codified landing pads for chromatin remodeling proteins. When David Allis of Rockefeller University talks about it it?s darn near impossible not to be infected by his enthusiasm. His was the first presentation this morning and he spoke of a protein that recognized Lysine 4 on histone H3 when it?s methylated, not once, not twice, but thrice. The protein contains a PHD finger to recognize the trimethylation and a BROMO domain which is known to recognize acetylated lysines. In his more speculative moments he posited that the shape of the protein indicates that it might be reading two marks on the same histone simultaneously, or even more tantalizingly, marks on different histones. Kevin Morris was one of two speakers exploring how RNA interference pathways feed into the histone modification and chromatin restructuring story. The gene for EF1a in human cells can be transcriptionally muted by RNA transcripts that get diced, sliced, and processed into the argonaute complex. Methylation may help in the process. The new wrinkle he found is that antisense transcripts appear to drive the silencing much better than sense transcripts. He offered a mechanism, but it was understandably hard to follow. ?I blew through this talk because there?s about two feet of fresh powder out there,? he said, letting class out early to hit the slopes. In this first day of the meeting, dedicated almost solely to chromatin structure, Ueli complained that while such modifications are good examples of signal transduction and transcriptional regulation, the interactions don?t meet the criteria of being epigenetics because they?re dynamic and transient not long standing and heritable like DNA methylation (on which he works in plants). But with a shrug, he?s happy that there?s good science being presented. Indeed when the snow?s this great, there should be room for everyone on the mountain.**Note:** In addition to apologizing for rushing through his talk, Kevin Morris corrected me on the assumption I make above that dicer and slicer are at work in his model. See this linkurl:later post;http://www.the-scientist.com/blog/display/23002/ for more.

Tangled up in Keystone

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