Cbx2 stably associates with mitotic chromosomes via a PRC2- or PRC1-independent mechanism and is needed for recruiting PRC1 complex to mitotic chromosomes
نویسندگان
چکیده
Polycomb group (PcG) proteins are epigenetic transcriptional factors that repress key developmental regulators and maintain cellular identity through mitosis via a poorly understood mechanism. Using quantitative live-cell imaging in mouse ES cells and tumor cells, we demonstrate that, although Polycomb repressive complex (PRC) 1 proteins (Cbx-family proteins, Ring1b, Mel18, and Phc1) exhibit variable capacities of association with mitotic chromosomes, Cbx2 overwhelmingly binds to mitotic chromosomes. The recruitment of Cbx2 to mitotic chromosomes is independent of PRC1 or PRC2, and Cbx2 is needed to recruit PRC1 complex to mitotic chromosomes. Quantitative fluorescence recovery after photobleaching analysis indicates that PRC1 proteins rapidly exchange at interphasic chromatin. On entry into mitosis, Cbx2, Ring1b, Mel18, and Phc1 proteins become immobilized at mitotic chromosomes, whereas other Cbx-family proteins dynamically bind to mitotic chromosomes. Depletion of PRC1 or PRC2 protein has no effect on the immobilization of Cbx2 on mitotic chromosomes. We find that the N-terminus of Cbx2 is needed for its recruitment to mitotic chromosomes, whereas the C-terminus is required for its immobilization. Thus these results provide fundamental insights into the molecular mechanisms of epigenetic inheritance.
منابع مشابه
Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY body in the pachytene spermatocytes.
The product of the Scmh1 gene, a mammalian homolog of Drosophila Sex comb on midleg, is a constituent of the mammalian Polycomb repressive complexes 1 (Prc1). We have identified Scmh1 as an indispensable component of the Prc1. During progression through pachytene, Scmh1 was shown to be excluded from the XY body at late pachytene, together with other Prc1 components such as Phc1, Phc2, Rnf110 (P...
متن کاملPolycomb repressive complex 2 (PRC2) suppresses Em-myc lymphoma
Polycomb group (PcG) proteins are global transcriptional repressors first identified in Drosophila as silencers of Hox genes during development. Subsequent genomewide studies showed that PcG proteins regulate genes involved in diverse cellular functions. PcG proteins exist in 2 distinct protein complexes called polycomb repressive complex 1 (PRC1) and 2 (PRC2). Mammalian PRC1 components include...
متن کاملPlk1 negatively regulates PRC1 to prevent premature midzone formation before cytokinesis
To achieve mitosis and cytokinesis, microtubules must assemble into distinct structures at different stages of cell division-mitotic spindles to segregate the chromosomes before anaphase and midzones to keep sister genomes apart and guide the cleavage furrow after anaphase. This temporal regulation is believed to involve Cdk1 kinase, which is inactivated in a switch-like way after anaphase. We ...
متن کاملDirect interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle
During animal cell division, the central spindle, an anti-parallel microtubule bundle structure formed between segregating chromosomes during anaphase, cooperates with astral microtubules to position the cleavage furrow. Because the central spindle is the only structure linking the two halves of the mitotic spindle, it is under mechanical tension from dynein-generated cortical pulling forces, w...
متن کاملMarking and Measuring Single Microtubules by PRC1 and Kinesin-4
Error-free cell division depends on the assembly of the spindle midzone, a specialized array of overlapping microtubules that emerges between segregating chromosomes during anaphase. The molecular mechanisms by which a subset of dynamic microtubules from the metaphase spindle are selected and organized into a stable midzone array are poorly understood. Here, we show using in vitro reconstitutio...
متن کامل