Human POGZ modulates dissociation of HP1α from mitotic chromosome arms through Aurora B activation

Abstract

Heterochromatin protein 1 (HP1) has an essential role in heterochromatin formation and mitotic progression through its interaction with various proteins. We have identified a unique HP1alpha-binding protein, POGZ (pogo transposable element-derived protein with zinc finger domain), using an advanced proteomics approach. Proteins generally interact with HP1 through a PxVxL (where x is any amino-acid residue) motif; however, POGZ was found to bind to HP1alpha through a zinc-finger-like motif. Binding by POGZ, mediated through its zinc-finger-like motif, competed with PxVxL proteins and destabilized the HP1alpha-chromatin interaction. Depletion experiments confirmed that the POGZ HP1-binding domain is essential for normal mitotic progression and dissociation of HP1alpha from mitotic chromosome arms. Furthermore, POGZ is required for the correct activation and dissociation of Aurora B kinase from chromosome arms during M phase. These results reveal POGZ as an essential protein that links HP1alpha dissociation with Aurora B kinase activation during mitosis.

Differential contribution of HP1 proteins to DNA end resection and homology-directed repair

“…Upon knockdown of each HP1 paralog, we observed that HP1α and β promoted SCEs role is most likely linked to a different process. More insights into the molecular mechanisms can be anticipated soon, since several new interactors have been recently identified for HP1 proteins, 9,10 including proteins involved in sister chromatid cohesion such as the cohesins loader NIPBL. In addition, HP1γ specifically interacts with TIN2, a central component of the shelterin complex, an interaction important to promote telomeric cohesion.…”

“…8 Maintenance pathways exploit the interaction of HP1 N-terminal chromodomain (CD) with histone H3 tri-methylated on Lysine 9 (H3K9me3), a modification that is highly enriched in heterochromatin, 7 as well as its capacity to homoand hetero-dimerize via its C-terminal chromoshadow domain (CSD). In addition, several HP1 partners 9,10 bind to the interface between two CSDs, which promote the activity of HP1 paralogs in various nuclear processes, such as transcriptional activation heterochromatin protein 1 paralogs (hp1α, β and γ in mammals) are not only central in heterochromatin organization, but have also been linked to transcriptional activation at euchromatic regions, maintenance of telomere stability and, most recently, to the DNa damage response (DDR). however, how hp1 proteins contribute to the DDR at a molecular level, and whether hp1 paralogs within the same organism, as well as their respective orthologs, have overlapping or unique roles in the DDR, remain to be elucidated.…”

Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif

“…This domain is typically present in enzymes that catalyse DNA cleavage followed by a strand transfer reaction. PogZ regulates the Aurora B kinase through interaction with heterochromatin protein 1, which is required for correct chromosome segregation during mitosis 37 . Like the HIV pre-integration and MLL1-menin complexes, JPO2 and PogZ are tethered to chromatin by LEDGF/p75 (refs 30,31,33).…”

Beyond the histone tale: HP1α deregulation in breast cancer epigenetics

“…43 However, there are proteins that associate with the CSD of HP1 through alternative sequence motifs, such as BRM-related gene 1 (BRG1) and pogo transposable element-derived protein with zinc finger domain (POGZ). 27,44 Interaction without requirement of the PxVxL motif is also observed for suppressor of variegation 3-9 homolog 1 (SUV39h1), 45 one of the best described interaction partners of HP1 proteins. The CSD also interacts with the first helix of the histone fold of H3, a region involved in chromatin remodeling.…”