Heun lab paper featured in Nature Communications. Image The histone CENP-A serves as the epigenetic mark for centromere identity. Transcription at the centromere leads to chromatin remodelling, and thereby offers the opportunity for new CENP-A loading, likely by removal of older placeholder histones. However, these structural rearrangements also pose a threat for retaining old CENP-A. Here, the Heun lab and collaborators show that maintenance of the centromeric mark is preserved by Spt6, which recycles CENP-A nucleosomes. Authors Bobkov, G.O.M, Huang, A., van den Berg. S.J.W., Mitra, S., Anselm, E., Lazou, V., Schunter, S., Feederle, R., Imhof, A., Lusser, A., Jansen, L.E.T., and Heun, P. Summary of Paper by Lori Koch Each chromosome has a specialised region called the centromere where, during cell division, it associates with dynamic fibres of the mitotic spindle. The centromere is defined by the protein CENP-A, a variant of the canonical histone H3, which must remain associated with the centromere through successive cell divisions. Research suggests that active transcription at the centromere affects the amount of CENP-A found there, possibly by evicting H3 histones to make room for loading of new CENP-A. Scientists in Patrick Heun’s lab (WCB), among others, identified that the protein Spt6 co-purifies with CENP-A isolated from cells. Spt6 is a histone chaperone that promotes elongation of RNA polymerase II during the process of transcription. In their recent study published in Nature Communications, the Heun lab investigated the role of Spt6 in the maintenance of CENP-A at the centromere in fly and human cells. Using microscopy and chemical labelling, they found that Spt6 co-localised with ongoing transcription at the centromere. Next, they found that depletion of Spt6 by RNAi or protein degradation induced lagging chromosomes and also led to reduced levels of CENP-A at centromeres. They used a dynamic protein marking strategy to find that this was due to a reduction in “old” CENP-A protein at the centromere rather than lack of “new” CENP-A incorporation during a single cell division cycle. Interestingly, they found that the acidic N-terminus of Spt6 binds to CENP-A directly in vitro and that this association is weakened by mimicking phosphorylation of CENP-A. Together, their results suggest that Spt6 ensures CENP-A is maintained at the centromere despite the structural rearrangements and histone eviction caused by active transcription. Related links Journal Link Heun Lab Website DOI This article was published on 2024-06-17
