PRMT6-mediated H3R2me2a guides Aurora B to chromosome arms for proper chromosome segregation

Nature Communications volume, 2020

Enjoy this exciting article by Kim et. al that was recently published in Nature Communications. The authors were finally able to show that H3R2me2a is the key histone mark for CPC recruitment onto mitotic chromosomes. Furthermore, results of this work support the interesting concept of arginine methylation as a dynamic process.

Abstract

The kinase Aurora B forms the chromosomal passenger complex (CPC) together with Borealin, INCENP, and Survivin to mediate chromosome condensation, the correction of erroneous spindle-kinetochore attachments, and cytokinesis. Phosphorylation of histone H3 Thr3 by Haspin kinase and of histone H2A Thr120 by Bub1 concentrates the CPC at the centromere. However, how the CPC is recruited to chromosome arms upon mitotic entry is unknown. Here, we show that asymmetric dimethylation at Arg2 on histone H3 (H3R2me2a) by protein arginine methyltransferase 6 (PRMT6) recruits the CPC to chromosome arms and facilitates histone H3S10 phosphorylation by Aurora B for chromosome condensation. Furthermore, in vitro assays show that Aurora B preferentially binds to the H3 peptide containing H3R2me2a and phosphorylates H3S10. Our findings indicate that the long-awaited key histone mark for CPC recruitment onto mitotic chromosomes is H3R2me2a, which is indispensable for maintaining appropriate CPC levels in dynamic translocation throughout mitosis.

Hec1 (9G3.23) GTX70268 and Mouse IgG antibody (HRP) GTX213111-01, manufactured by our long-term and trusted partner GeneTex, were used in this work.