The defining feature of centromeres is the presence of a protein called CenH3, but how this specialized histone gets to centromeres and stays there has been a mystery. Perpelescu et al. bring us one step closer to unraveling the mystery with their discovery that a chromatin remodeling protein called RSF stabilizes CENP-A (the human CenH3) at centromeres.
The expansive DNA strands of the genome are wrapped at regular intervals around nucleosomes to ensure orderly packaging. Everywhere besides centromeres, these nucleosomes contain histone H3. At centromeres they contain the related protein CenH3. When DNA is replicated new nucleosomes must be incorporated into the daughter strands. H3 nucleosomes are added immediately, but the loading of CenH3 nucleosomes is delayed until after cell division.
During this incorporation interval, CENP-A and RSF colocalized at centromeres, the team showed. The arrival of RSF at centromeres followed the arrival of CENP-A very slightly, suggesting RSF does not chaperone CENP-A to its chromatin home. Instead RSF appears to stabilize CENP-A's incorporation—without RSF the amount of stably associated CENP-A in chromatin was decreased. The next step is to identify CENP-A's chaperone(s) and the signals that recruit RSF.