For the past couple of days representatives from BMG LABTECH have been in attendance at Discovery on Target in Boston, MA, USA. Here, we have learned more about epigenetics, which continues to grow in importance as the scientific community understands more about how epigenetics occurs and is regulated. Central to epigenetics is the post-translational modification of histones which plays a role in determining what genes will be transcribed into RNA and eventually translated into protein.
|Cartoon diagram of an epigenetic reader binding to an|
acetylated lysine in a histone tail
The proteins that are involved in epigenetics based on histone modification are broadly categorized into three groups. Writers and erasers which add and remove the post-translational modifications as well as readers which detect the modification and are often part of a multi-protein complex which interpret the modification and lead to a change in gene expression. These readers have been studied more avidly in recent years and many presentations and discussions at this conference have indicated the importance of readers in normal function. Furthermore, alterations of readers are associated with several disease states and they have emerged as new druggable targets.
In the simplest of terms the interaction between a modified histone tail and an epigenetic reader is a protein-protein interaction. As such it is not surprising that approaches that have been previously successful in elucidating protein-protein interactions have been applied to this field. This includes, but is not limited to fluorescence polarization and AlphaScreen. As BMG microplate readers, such as the PHERAstar FS and the new CLARIOstar, have been shown to perform these types of analyses well, they should be considered excellent tools for investigating the function of epigenetic readers.
One talk of particular note was by Danette Daniels, PhD, from Promega. Dr. Daniels described the combination of NanoLuc labeling of a bromodomain protein (an epigenetic reader) and fluorescent labeling of histone. In this way they can tell when the epigenetic reader is bound to histone in live cells through the use of BRET. This data was also recently shared in a BMG hosted webinar which showed that the new CLARIOstar is the only microplate reader with a monochromator that was sensitive enough to detect the NanoLuc BRET signal.
We are very glad that we have had the opportunity to attend Discovery on Target and meet with so many great scientists. We look forward to the remainder of the conference and hope that BMG can help you in your drug discovery program!