Not to get all “Oprah”, but sometimes, you need to let go of unstable elements in order to enhance your life. Researchers now report that this drama unfolds at the DNA level too. Here’s what they found: an unstable nucleosome sitting smack dab in the center of an enhancer can get kicked off to make way for transcription factors and gene expression. (We’re all teary-eyed just thinking about it.) The team also showed that this phenomenon happens to many enhancers.
To get to the core of nucleosome positioning at enhancers, the team used nucleosome-resolution chromatin immunoprecipitation deep sequencing (ChIP-Seq) to look at H3K4 methylation (specifically the mono, di and tri flavors) in prostate cancer cells (LNCaP) stimulated by the androgen receptor agonist 5-α-dihydrotestosterone (DHT).
Unstimulated cells had two well-positioned H3K4me2 nucleosomes on either side of the enhancer and one H3K4me2 nucelosome in the center. When DHT was added, however, H3K4me2 signal increased in the flanking regions, but decreased in the center of the enhancer. It turns out that the central nucleosome was more likely to contain the labile H2A.Z variant and was more likely to have lots of A/Ts wound around it than the neighboring nucleosomes, which may help explain why it was not that stable.
In the process of running these experiments, a new model and method for predicting enhancers was born. The Nucleosome Stabilization-Destabilization (NSD) score accurately IDs transcription binding sites. NSD was able to validate the androgen binding site that they were looking at, and in addition could predict unknown binding sites as well, making it a powerful tool for the study of transcription enhancers.
See if NSD can enhance your enhancer experiments, check out the full article at Nature Genetics, March 2010.