The long and the short of it: linker histone H1 is required for metaphase chromosome compaction.

Faithful distribution of the genome to daughter cells requires that replicated chromatids are compacted and resolved from one another, and that functional kinetochores assemble at their centromeres to mediate spindle interactions. A molecular and mechanistic understanding of these critical processes is far from complete. We discovered that linker histone H1, a major chromatin component, is required for longitudinal compaction of replicated sperm chromosome arms in Xenopus laevis egg extracts that recapitulate the cell cycle in vitro. Due to their elongated structure, H1-depleted chromosomes could not be aligned or segregated by the spindle despite apparently normal kinetochore assembly. Interestingly, enrichment of H1 onto chromatin required passage through interphase, when DNA replication takes place. Here we show that interphase-dependent loading is also a feature of kinetochore components including Ndc80. Thus, linker histone H1 contributes to chromosome condensation in vertebrates, and important molecular determinants of mitotic chromosome and kinetochore structure and function are established during interphase.