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

• Published in: Nature communications Vol. 11; no. 1; p. 612
• Main Authors: Kim, Seul, Kim, Nam Hyun, Park, Ji Eun, Hwang, Jee Won, Myung, Nayeon, Hwang, Ki-Tae, Kim, Young A, Jang, Chang-Young, Kim, Yong Kee
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.01.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13/105; 13/109; 13/51; 13/89; 14/1; 14/63; 631/337; 631/67; 631/80; 631/80/641/1655; 96/95; Amino Acid Sequence; Arginine; Arginine - metabolism; Aurora B protein; Aurora Kinase B - metabolism; Breast Neoplasms - pathology; Cell division; Centromere - metabolism; Chromosomal Proteins, Non-Histone - metabolism; Chromosome Segregation; Chromosomes; Chromosomes, Human - metabolism; Cytokinesis; Demethylation; Disease Progression; Female; HeLa Cells; Histone H2A; Histone H3; Histones; Histones - chemistry; Histones - metabolism; Humanities and Social Sciences; Humans; INCENP protein; Kinases; MCF-7 Cells; Methylation; Mitosis; multidisciplinary; Nuclear Proteins - metabolism; Passengers; Phosphorylation; Protein arginine methyltransferase; Protein-Arginine N-Methyltransferases - metabolism; Proteins; RNA, Small Interfering - metabolism; Science; Science (multidisciplinary); Survivin; Translocation; Yeast
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-14511-w

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. The proteins of the chromosomal passenger complex help chromosomes condense before cell division, but how this complex arrives at chromosomes was not known. Here the authors show that PRMT6 methylates histone H3 to recruit the chromosomal passenger complex.