Today’s Special Presidential Lecture was such a treat! Every once in a while, we’re lucky enough to find something which engages us such that as we listen, we find ourselves almost literally sitting at the edge of our seat… hanging on to every word in an effort not to miss anything.
[image above taken from: “The Hidden Life of our Genes” movie]
Paolo Sassone-Corsi began his lecture entitled: “Joining the dots: Epigenetics, Plasticity and the Circadian Clock” by introducing Conrad Waddington’s term “Epigenetic Landscape” The idea is that cells with the same initial genomic profile develop into distinct cellular subtypes. The metaphor is that of marbles on a hill, where the marbles are the cells and the landscape of peaks and valleys represents an added layer of regulation (in this case: epigenetics).
It’s the “path” which the marble takes down the ridges and valleys of the landscape which determine the “fate” of the marble (i.e. where it will end up = what kind of cell it finally becomes). Won’t discuss this in this post: but one can see how the marbles going “back up the hill” then corresponds to the re-programming of stem-cells back to their “pluripotent” state.
After reviewing the structure of DNA, chromatin and epigenetic marks, and the ideas of Waddington, Sassone-Corsi began to paint the audience a picture of how what we traditionally understand and refer to as epigenetics, works in concert with circadian-regulated mechanisms in the body in order to increase or decrease plasticity.
“At least 10-15% of all cellular transcripts oscillate in a circadian manner,” he noted and “most of these are CCGs.” He went on to explain that this indicates a larger mechanism of regulation at play. In other words, epigenetics had to be involved. In their investigation of how circadian rhythms and epigenomic expression were coupled, they discovered that SIRT1, a nicotinamide adenin dinucleotide (NAD(+))-dependent HDAC, functioned in a circadian manner.
If SIRT1 sounds familiar – it’s because it’s found in red wine and is known to regulate aging, inflammation and metabolic processes. “It’s the French paradox,” he said “the French eat fatty foods and are still healthy because they drink red wine.” Don’t get your hopes up, though. He was quick to say, “this doesn’t mean you should drink too much!”
There’s a lot more detail and ground I’m not covering here – but I’m pretty sure I hit the main points. Here’s an excerpt from one of his abstracts: “Accumulating data show that chromatin remodeling events may be critical for providing specificity and plasticity in circadian regulation, and metabolic cues may be involved in directing such epigenetic events.”
I’m going to have to sit down and read his actual papers after the SfN meeting rush is over, to fully appreciate and grasp the implications of these findings. I encourage you to do the same! More blog posts on this topic are sure to be upcoming…