Local chromatin decompaction shapes mitotic chromosome landscape

Unregulated activation of transcription on mitotic chromosomal arms can be detrimental to faithful chromosome segregation1-3, although a subset of genes are up-regulated during mitosis4, raising the question as to how gene activation is coordinated in the context of mitotic chromosome reorganization. Here we investigate the fine structure of mitotic chromosomes in fission yeast Schizosaccharomyces pombe and reveal that intense decompaction of local chromatin upon mitotic gene activation helps shape the mitotic chromosome landscape. More specifically, we show that binding of mitosis-specific transcription factors, Ace2 and MluI binding factor (MBF)5,6, to gene promoters followed by transcriptional elongation can locally induce chromatin decompaction during mitosis. Interestingly, local decompaction-competent genes can establish chromatin boundaries that demarcate long-range contact domains, indicating tight coupling between local and global genome organizations. Furthermore, efficient local decompaction requires enough transcriptional elongation distance and histone removal, providing a mechanistic insight into the decompaction-associated domain boundary formation. Given that the demarcation of large, self-associating domains is critical for faithful chromosome segregation7, we propose that decompaction-competent genes can be a key determinant of mitotic chromosome configuration, thereby underpinning the maintenance of genome integrity over generations, and thus their distribution along chromosomes can be subject to evolutionary selection.