The role of the Aurora B kinase in mediating cellular functions outside
mitosis was investigated. A SILAC-based approach was used to show that
Aurora B interacts with proteins implicated in gene regulation and chromatin
organization in G1 activated B cells. Among these interactors, I identified the
PRC1 component Ring1B as a new partner of Aurora B. Both proteins are bound
to the promoters of highly expressed genes in resting B and T lymphocytes.
Quiescent resting B cells require the maintenance of a transcriptional programme
that keeps the cells viable and ready to proliferate upon encounter with a specific
antigen. Aurora B and Ring1B physically co-occupy the same promoters in
resting B cells but, upon activation, Aurora B is replaced by MSK1 on its target
genes, whereas Ring1B binding is preserved.
Analysis of the active promoters in resting B cells shows that other PRC1
components, such as Cbx7 and Bmi1, and the histone deubiquitinase USP16,
together with Aurora B and Ring1B, bind almost exclusively to the regulatory
elements of active promoters and are not found at repressed genes. Binding of
PRC2 components and deposition of the H3K27me3 and H2Aubq marks are
largely confined to silent genes. By employing conditional knockout mouse
models, I showed that removal of either Aurora B or Ring1B results in a global
reduction in the binding of unphosphorylated and serine 5-phosphorylated RNA
Polymerase II to active promoters. This phenomenon is also accompanied by a
reduction in the production of transcripts from Aurora B and Ring1B target genes
and reduced cell viability. Aurora B is also required to maintain high levels of
phosphorylated H3S28 and low levels of the repressive H2Aubq mark at active
promoters. These results identify a new role for both Aurora B and Ring1B in the
regulation of active transcription in quiescent lymphocytes
