Abstract
Although the formation of rod-shaped chromosomes is vital for the correct segregation of eukaryotic genomes during cell divisions, the molecular mechanisms that control the chromosome condensation process have remained largely unknown. Here, we identify the C2H2 zinc-finger transcription factor Zas1 as a key regulator of mitotic condensation dynamics in a quantitative live-cell microscopy screen of the fission yeast Schizosaccharomyces pombe By binding to specific DNA target sequences in their promoter regions, Zas1 controls expression of the Cnd1 subunit of the condensin protein complex and several other target genes, whose combined misregulation in zas1 mutants results in defects in chromosome condensation and segregation. Genetic and biochemical analysis reveals an evolutionarily conserved transactivation domain motif in Zas1 that is pivotal to its function in gene regulation. Our results suggest that this motif, together with the Zas1 C-terminal helical domain to which it binds, creates a cis/trans switch module for transcriptional regulation of genes that control chromosome condensation.
Highlights
The reshaping of interphase chromatin into rod-shaped mitotic and meiotic chromosomes is one of the most remarkable events in the eukaryotic cell cycle
Mutations in the zas1 gene slow down chromosome condensation dynamics To search for factors that control chromosome condensation dynamics, we screened datasets of ∼1,100 randomly generated temperature-sensitive fission yeast strains for mutants that displayed alterations in the dynamics of chromosome condensation (Petrova et al, 2013)
The Zas1 transcription factors (TFs) controls chromosome condensation dynamics In this study, we identified the ZF TF Zas1 as a key regulator of mitotic chromosome condensation dynamics in fission yeast and demonstrated that it controls the expression of a specific set of genes, including the cnd1 gene that encodes one of the two HEAT-repeat subunits of the condensin complex
Summary
The reshaping of interphase chromatin into rod-shaped mitotic and meiotic chromosomes is one of the most remarkable events in the eukaryotic cell cycle. Even though the phenomenology of the chromosome condensation process had been well described by the end of the 19th century (Flemming, 1882), our understanding of the molecular mechanisms that drive the massive changes in chromatin organization has remained surprisingly limited (Moser and Swedlow, 2011). This is largely because, despite the identification by proteomic studies of thousands of proteins that associate with mitotic chromosomes (Ohta et al, 2010), only very few of these proteins seem to have clearly defined roles in the formation of mitotic chromosomes. Whereas the Cnd subunit functions in the recruitment of condensin complexes to chromosomes by creating a DNA binding site together with Cnd (Kschonsak et al, 2017), the function of Cnd has remained unknown
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