Every auto enthusiast knows that if you want to maximize the performance of your car, you’ve got to have the right parts in the right combination. While sometimes you may have to completely rebuild your engine, other times all you need is to upgrade to the latest system components. In a recent article published in Molecular Cell, researchers in the lab of C. David Allis find that histone crotonylation, the newest upgrade in the chromatin industry, boosts transcription to a greater degree than the already well-studied acetylation mark.
The story of crotonylation began in 2011 with a paper from the lab of Yingming Zhao when they discovered it as a novel histone modification on lysine residues. The Zhao lab showed histone crotonylation correlated well with gene expression and marked promoters and enhancers just like its close cousin, acetylation. Whether it had a direct role in transcription, however, was unknown.
Following up, C. David Allis and his team find that histone crotonylation indeed has a direct role in stimulating transcription to a greater extent than acetylation. Furthermore, they show that:
- p300 is able to catalyze both histone crotonylation and acetylation with the primary site of crotonylation being H3K18.
- The concentration of the metabolite crotonyl-coA determines global levels of histone crotonylation both in vitro and in vivo.
- The metabolic enzyme ACSS2 regulates the levels of crotonyl-coA and hence crotonylation.
The researchers also turned to a transcriptional activation model in mouse macrophages to study the effect of altering crotonylation levels. Interestingly, they show that increasing the levels of crotonyl-coA leads to increased crotonylation and consequently increased transcription of LPS-activated genes.
Although the mechanism by which crotonylation further stimulates transcription still eludes the authors, they have provided yet another intimate link between metabolism, histone modifications and transcription that is sure to inspire more studies.
Get the details of this epigenetic transcriptional booster over in Molecular Cell, April 2015.