Abstract
Chromosome condensation is a hallmark of mitosis in eukaryotes and is a prerequisite for faithful segregation of genetic material to daughter cells. Here we show that condensin, which is essential for assembling condensed chromosomes, helps to preclude the detrimental effects of gene transcription on mitotic condensation. ChIP-seq profiling reveals that the fission yeast condensin preferentially binds to active protein-coding genes in a transcription-dependent manner during mitosis. Pharmacological and genetic attenuation of transcription largely rescue bulk chromosome segregation defects observed in condensin mutants. We also demonstrate that condensin is associated with and reduces unwound DNA segments generated by transcription, providing a direct link between an in vitro activity of condensin and its in vivo function. The human condensin isoform condensin I also binds to unwound DNA regions at the transcription start sites of active genes, implying that our findings uncover a fundamental feature of condensin complexes.
Highlights
Chromosome condensation is a hallmark of mitosis in eukaryotes and is a prerequisite for faithful segregation of genetic material to daughter cells
Quantitative PCR measurements at multiple genomic loci of ChIP-purified DNA from wild-type or condensin mutant cells verified that binding in the ChIP-seq profile was quantitatively accurate and relied on the functional integrity of the condensin complex (Fig. 1b,c and Supplementary Fig. 1d,e)
It should be noted that these profiles do not indicate that condensin was absent from regions other than the detected peaks. The results of both ChIP-seq and ChIP-quantitative PCR (qPCR) show that a significant amount of condensin was found along the entire nuclear genome, it was more prominent at the peaks (Supplementary Fig. 1d,f)
Summary
Chromosome condensation is a hallmark of mitosis in eukaryotes and is a prerequisite for faithful segregation of genetic material to daughter cells. We demonstrate that condensin is associated with and reduces unwound DNA segments generated by transcription, providing a direct link between an in vitro activity of condensin and its in vivo function. Recent work[15,16] has revealed an association of condensin I and II complexes with transcribed genes in chicken and Caenorhabditis elegans chromosomes, respectively, providing valuable insight into this question. It remains to be elucidated, how condensin functions at its binding sites. Parallel sequencing has since become available and offers an opportunity to re-examine the distribution profile of condensin binding, as it enables more sensitive and accurate identification of DNA fragments
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