Topoisomerase activity is linked to altered nucleosome positioning and transcriptional regulation in the fission yeast fbp1 gene

Abstract

Chromatin structure, including nucleosome positioning, has a fundamental role in transcriptional regulation through influencing protein-DNA interactions. DNA topology is known to influence chromatin structure, and in doing so, can also alter transcription. However, detailed mechanism(s) linking transcriptional regulation events to chromatin structure that is regulated by changes in DNA topology remain to be well defined. Here we demonstrate that nucleosome positioning and transcriptional output from the fission yeastfbp1andprp3genes are altered by excess topoisomerase activity. Given that lncRNAs (longnoncoding RNAs) are transcribed from thefbp1upstream region and are important forfbp1gene expression, we hypothesized that local changes in DNA topological state caused by topoisomerase activity could alter lncRNA andfbp1transcription. In support of this, we found that topoisomerase overexpression caused destabilization of positioned nucleosomes within thefbp1promoter region, which was accompanied by aberrantfbp1transcription. Similarly, the direct recruitment of topoisomerase, but not a catalytically inactive form, to the promoter region offbp1caused local changes in nucleosome positioning that was also accompanied by alteredfbp1transcription. These data indicate that changes in DNA topological state induced by topoisomerase activity could lead to alteredfbp1transcription through modulating nucleosome positioning.