A Transient Rise in Free Mg2+ Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation

• Published in: Current biology 2018-02, Vol.28 (3), p.444-451.e6
• Main Authors: Maeshima, Kazuhiro, Matsuda, Tomoki, Shindo, Yutaka, Imamura, Hiromi, Tamura, Sachiko, Imai, Ryosuke, Kawakami, Syoji, Nagashima, Ryosuke, Soga, Tomoyoshi, Noji, Hiroyuki, Oka, Kotaro, Nagai, Takeharu
• Format: Article
• Language: English
• Subjects: ATP; Ca2; chromosome condensation; condensin; FRET; indicator; live-cell imaging; Mg2; mitotic chromosome; nucleosome
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2017.12.035

For cell division, negatively charged chromatin, in which nucleosome fibers (10 nm fibers) are irregularly folded [1–5], must be condensed into chromosomes and segregated. While condensin and other proteins are critical for organizing chromatin into the appropriate chromosome shape [6–17], free divalent cations such as Mg2+ and Ca2+, which condense chromatin or chromosomes in vitro [18–28], have long been considered important, especially for local condensation, because the nucleosome fiber has a net negative charge and is by itself stretched like “beads on a string” by electrostatic repulsion. For further folding, other positively charged factors are required to decrease the charge and repulsion [29]. However, technical limitations to measure intracellular free divalent cations, but not total cations [30], especially Mg2+, have prevented us from elucidating their function. Here, we developed a Förster resonance energy transfer (FRET)-based Mg2+ indicator that monitors free Mg2+ dynamics throughout the cell cycle. By combining this indicator with Ca2+ [31] and adenosine triphosphate (ATP) [32] indicators, we demonstrate that the levels of free Mg2+, but not Ca2+, increase during mitosis. The Mg2+ increase is coupled with a decrease in ATP, which is normally bound to Mg2+ in the cell [33]. ATP inhibited Mg2+-dependent chromatin condensation in vitro. Chelating Mg2+ induced mitotic cell arrest and chromosome decondensation, while ATP reduction had the opposite effect. Our results suggest that ATP-bound Mg2+ is released by ATP hydrolysis and contributes to mitotic chromosome condensation with increased rigidity, suggesting a novel regulatory mechanism for higher-order chromatin organization by the intracellular Mg2+-ATP balance. [Display omitted] •We developed a FRET-based Mg2+ indicator for live cell-cycle analysis•During mitosis, levels of free Mg2+ increase and are coupled with a decrease in ATP•ATP reduction induced chromosome hypercondensation•Chelating Mg2+ had a chromosome decondensation effect How the negatively charged long genomic DNA is organized into mitotic chromosome remains unclear. Using a newly developed Mg2+ indicator, Maeshima et al. demonstrate a transient rise in free Mg2+ released from ATP-Mg during mitosis and suggest that the rise contributes to mitotic chromosome condensation by charge neutralization.