Nuclear partitioning by surface condensation on metaphase chromatids

Abstract

Protein partitioning between the nucleus and the cytoplasm is a defining feature of eukaryotic cells, and it is thought to be primarily regulated by transport across the nuclear envelope1-3. However, during early vertebrate development, ensuring accurate nuclear composition is challenging due to dramatic changes in cell size and rapid cell division4-7. Here, we show that the embryonic linker histone H1.8 is rapidly partitioned into the nucleus through a nuclear import-independent mechanism. In the cytoplasm of Xenopus laevis egg extracts, prior to nuclear assembly, H1.8 condenses on the surface of chromatids as droplets that partially wet them. Simultaneously, H1.8 also forms condensates in the cytoplasm that buffer the condensate nucleation rate on the chromatid surface, resulting in a nuclear partitioning that is independent of the DNA-to-cytoplasm ratio. To show the generality of the surface condensation mechanism, we extended our study to Nucleophosmin 1 (NPM1) in human cell culture. Similar to H1.8, NPM1 forms a layer around chromatids that breaks into droplets that subsequently are incorporated into the nucleus. Our findings show that the properties of condensate wetting and nucleation on chromatid surfaces provide an alternative and robust biophysical mechanism to regulate nuclear composition.