How to get to know your neighbors, if you are a protein

In in a shared flat, you build up different relationships with each of your flat mates and some of them can be quite complicated. Similarly, proteins within the nucleus of a cell have complex relationships with each other. However, in contrast to flat mates, these protein-protein interaction networks are essential. In a review article, Henning Ummethum and Dr. Stephan Hamperl of the Institute of Epigenetics and Stem cells give important insight into the recently established approach “proximity labeling” that is used to get to know the neighborhood of the protein of interest, in particular in the context of chromatin.

@Ummethum et al. 2020, Front Genet.

Our social life is complex with many interactions to different groups of people: friends, colleagues, flat mates, neighbors and so on. This social interaction network constantly changes over time. For example, in a shared flat, people are moving in and out and you may get to know many different people over time and also build up different kinds of relationships with them. Such high dynamics and fast changes also occur within the nucleus of our cells. For example, to pack the long range of DNA into the tiny nucleus, different proteins bind to the DNA and form a structure known as chromatin. However, to allow different processes that are essential for our cells without causing conflicts, the chromatin structure needs to be frequently rearranged. Similar to relying on your flat mates to split the rent, many proteins act together to regulate such chromatin rearrangements. Discovering these protein-protein interaction networks is fundamental to understand the structural and functional organization of chromatin. Conventional methods to uncover the relationships between proteins rely on a physical connection between two proteins that needs to ‘survive’ the harsh treatments required for the protein purification. In 2012, the technique termed ‘proximity labeling’ has been established and this technique has a big advantage compared to previous methods. During the procedure, all the neighboring proteins close to the protein of interest are labeled. Comparable to a shared flat where the flat mates have all the same address.

In a review article published recently in Frontiers in Genetics, the PhD student Henning Ummethum and his supervisor Dr. Stephan Hamperl from the Institute of Epigenetics and Stem Cells compare currently available proximity labeling approaches used to study chromatin interaction networks. They sum up the development and appliances of the techniques over the recent years and discuss how it has been successfully applied to characterize proteins that are close to specific chromatin factors, specific genomic loci or whole nuclear compartments.

@written by: Henning Ummethum

The review article is part of the research topic of Frontiers in Genetics “The Evolving Chromatin and Transcriptional Landscapes - Emerging Methods, Tools and Techniques

Original publication: Ummethum H, Hamperl S. (2020). Proximity labeling techniques to study chromatin. Frontiers in Genetics.