A novel role for the Aurora B kinase in epigenetic marking of silent chromatin in differentiated postmitotic cells.
Combinatorial modifications of the core histones have the potential to fine-tune the epigenetic regulation of chromatin states. The Aurora B kinase is responsible for generating the double histone H3 modification tri-methylated K9/phosphorylated S10 (H3K9me3/S10ph), which has been implicated in chromosome condensation during mitosis. In this study, we have identified a novel role for Aurora B in epigenetic marking of silent chromatin during cell differentiation. We find that phosphorylation of H3 S10 by Aurora B generates high levels of the double H3K9me3/S10ph modification in differentiated postmitotic cells and also results in delocalisation of HP1beta away from heterochromatin in terminally differentiated plasma cells. Microarray analysis of the H3K9me3/S10ph modification shows a striking increase in the modification across repressed genes during differentiation of mesenchymal stem cells. Our results provide evidence that the Aurora B kinase has a role in marking silent chromatin independently of the cell cycle and suggest that targeting of Aurora B-mediated phosphorylation of H3 S10 to repressed genes could be a mechanism for epigenetic silencing of gene expression.
Sabbattini
Pierangela
P
Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, UK. pierangela.sabbattini@csc.mrc.ac.uk <pierangela.sabbattini@csc.mrc.ac.uk>
Canzonetta
Claudia
C
Sjoberg
Marcela
M
Nikic
Svetlana
S
Georgiou
Andrew
A
Kemball-Cook
Geoffrey
G
Auner
Holger W
HW
Dillon
Niall
N
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006570:Heterochromatin / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013154:Spleen / Q000166:cytology
D006570:Heterochromatin; D006657:Histones; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases