by Georg Kustatscher, University of Edinburgh
Host: Sara Sdelci
In this seminar I will outline our efforts to explore aspects of chromatin biology by proteomics. I will present our method to enrich bulk chromatin for proteomic analyses and show how we used it to study the composition of chromatin – and how that changes as chromosomes condense during mitosis. In the second part of the talk I will introduce our work on the relationship between genome organisation and protein expression control. For example, in humans, 10% of protein-coding genes are transcribed from bidirectional promoters and many more are organised in larger clusters. Intriguingly, neighbouring genes are frequently coexpressed but rarely functionally related. We found that coexpression of bidirectional gene pairs, and closeby genes in general, is buffered at the protein level and therefore unlikely to serve a regulatory purpose. However, grouping genes together along the genome sequence or 3D structure is associated with reduced expression noise. In a second step, we demonstrate the implications of these findings for functional proteomics. We construct ProteomeHD, a large proteomics dataset documenting the response of 10,323 proteins to 294 biological perturbations, and use machine-learning to create a proteome co-regulation map that reveals detailed functional associations between human proteins.